CH367171A - Process for the production of new N, N-pentamethylene ureas - Google Patents
Process for the production of new N, N-pentamethylene ureasInfo
- Publication number
- CH367171A CH367171A CH6283158A CH6283158A CH367171A CH 367171 A CH367171 A CH 367171A CH 6283158 A CH6283158 A CH 6283158A CH 6283158 A CH6283158 A CH 6283158A CH 367171 A CH367171 A CH 367171A
- Authority
- CH
- Switzerland
- Prior art keywords
- piperidine
- ureas
- formula
- pentamethylene
- new
- Prior art date
Links
- 235000013877 carbamide Nutrition 0.000 title claims description 20
- 238000000034 method Methods 0.000 title claims description 5
- 238000004519 manufacturing process Methods 0.000 title description 6
- 150000001412 amines Chemical class 0.000 claims description 11
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 8
- 150000004649 carbonic acid derivatives Chemical class 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 150000004651 carbonic acid esters Chemical class 0.000 claims 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 22
- 150000003672 ureas Chemical class 0.000 description 9
- 239000004202 carbamide Substances 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- JEGMWWXJUXDNJN-UHFFFAOYSA-N 3-methylpiperidine Chemical compound CC1CCCNC1 JEGMWWXJUXDNJN-UHFFFAOYSA-N 0.000 description 5
- UZOFELREXGAFOI-UHFFFAOYSA-N 4-methylpiperidine Chemical compound CC1CCNCC1 UZOFELREXGAFOI-UHFFFAOYSA-N 0.000 description 5
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- YIIMEMSDCNDGTB-UHFFFAOYSA-N Dimethylcarbamoyl chloride Chemical compound CN(C)C(Cl)=O YIIMEMSDCNDGTB-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 3
- OFCCYDUUBNUJIB-UHFFFAOYSA-N n,n-diethylcarbamoyl chloride Chemical compound CCN(CC)C(Cl)=O OFCCYDUUBNUJIB-UHFFFAOYSA-N 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- YBJVMBCGVMNFQK-UHFFFAOYSA-N n,n-diethyl-4-methylpiperidine-1-carboxamide Chemical compound CCN(CC)C(=O)N1CCC(C)CC1 YBJVMBCGVMNFQK-UHFFFAOYSA-N 0.000 description 2
- CMUOJBJRZUHRMU-UHFFFAOYSA-N nitrourea Chemical compound NC(=O)N[N+]([O-])=O CMUOJBJRZUHRMU-UHFFFAOYSA-N 0.000 description 2
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 2
- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- LXXTVGKSGJADFU-UHFFFAOYSA-N (4-nitrophenyl)urea Chemical compound NC(=O)NC1=CC=C([N+]([O-])=O)C=C1 LXXTVGKSGJADFU-UHFFFAOYSA-N 0.000 description 1
- DNUTZBZXLPWRJG-UHFFFAOYSA-N 1-Piperidine carboxylic acid Chemical compound OC(=O)N1CCCCC1 DNUTZBZXLPWRJG-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
- GELXVDNNZSIRQA-UHFFFAOYSA-N 2,4,6-trimethylpiperidine Chemical compound CC1CC(C)NC(C)C1 GELXVDNNZSIRQA-UHFFFAOYSA-N 0.000 description 1
- QOZOFODNIBQPGN-UHFFFAOYSA-N 2,4-dimethylpiperidine Chemical compound CC1CCNC(C)C1 QOZOFODNIBQPGN-UHFFFAOYSA-N 0.000 description 1
- NNWUEBIEOFQMSS-UHFFFAOYSA-N 2-Methylpiperidine Chemical compound CC1CCCCN1 NNWUEBIEOFQMSS-UHFFFAOYSA-N 0.000 description 1
- OUWLXWZZZKYIIF-UHFFFAOYSA-N 2-methylpiperidine-1-carboxamide Chemical class CC1CCCCN1C(N)=O OUWLXWZZZKYIIF-UHFFFAOYSA-N 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- QUNRCNWRIOEOEM-UHFFFAOYSA-N 3-methylpiperidine-1-carbonyl chloride Chemical compound CC1CCCN(C(Cl)=O)C1 QUNRCNWRIOEOEM-UHFFFAOYSA-N 0.000 description 1
- YIEFSVGIBPISLM-UHFFFAOYSA-N 3-methylpiperidine-1-carboxylic acid Chemical compound CC1CCCN(C(O)=O)C1 YIEFSVGIBPISLM-UHFFFAOYSA-N 0.000 description 1
- VLJQDHDVZJXNQL-UHFFFAOYSA-N 4-methyl-n-(oxomethylidene)benzenesulfonamide Chemical compound CC1=CC=C(S(=O)(=O)N=C=O)C=C1 VLJQDHDVZJXNQL-UHFFFAOYSA-N 0.000 description 1
- GHRWHEKMYXUOGO-UHFFFAOYSA-N 4-methylpiperidin-1-ium;chloride Chemical compound Cl.CC1CCNCC1 GHRWHEKMYXUOGO-UHFFFAOYSA-N 0.000 description 1
- WRROPVUNDBWCQY-UHFFFAOYSA-N 4-methylpiperidine-1-carbonyl chloride Chemical compound CC1CCN(C(Cl)=O)CC1 WRROPVUNDBWCQY-UHFFFAOYSA-N 0.000 description 1
- VIRFRHVDXNAETH-UHFFFAOYSA-N 4-methylpiperidine-1-carboxylic acid Chemical compound CC1CCN(C(O)=O)CC1 VIRFRHVDXNAETH-UHFFFAOYSA-N 0.000 description 1
- CKDWPUIZGOQOOM-UHFFFAOYSA-N Carbamyl chloride Chemical compound NC(Cl)=O CKDWPUIZGOQOOM-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 239000004097 EU approved flavor enhancer Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- 206010000210 abortion Diseases 0.000 description 1
- 231100000176 abortion Toxicity 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 230000000507 anthelmentic effect Effects 0.000 description 1
- 239000000921 anthelmintic agent Substances 0.000 description 1
- ABBZJHFBQXYTLU-UHFFFAOYSA-N but-3-enamide Chemical compound NC(=O)CC=C ABBZJHFBQXYTLU-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000007859 condensation product Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- UZBQIPPOMKBLAS-UHFFFAOYSA-N diethylazanide Chemical compound CC[N-]CC UZBQIPPOMKBLAS-UHFFFAOYSA-N 0.000 description 1
- QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 description 1
- NLGBBTLIUDCAQF-UHFFFAOYSA-N dipropylcarbamic acid Chemical compound CCCN(C(O)=O)CCC NLGBBTLIUDCAQF-UHFFFAOYSA-N 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 235000019264 food flavour enhancer Nutrition 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 150000002730 mercury Chemical class 0.000 description 1
- HVIAVANLCAFGJD-UHFFFAOYSA-N n,n,4-trimethylpiperidine-1-carboxamide Chemical compound CC1CCN(C(=O)N(C)C)CC1 HVIAVANLCAFGJD-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
- SKJJGBRWKOFYAD-UHFFFAOYSA-N piperidin-1-ylurea Chemical compound NC(=O)NN1CCCCC1 SKJJGBRWKOFYAD-UHFFFAOYSA-N 0.000 description 1
- BIFDXOOJPDHKJH-UHFFFAOYSA-N piperidine-1-carbonyl chloride Chemical compound ClC(=O)N1CCCCC1 BIFDXOOJPDHKJH-UHFFFAOYSA-N 0.000 description 1
- JSPCTNUQYWIIOT-UHFFFAOYSA-N piperidine-1-carboxamide Chemical compound NC(=O)N1CCCCC1 JSPCTNUQYWIIOT-UHFFFAOYSA-N 0.000 description 1
- 230000008635 plant growth Effects 0.000 description 1
- CBPYOHALYYGNOE-UHFFFAOYSA-M potassium;3,5-dinitrobenzoate Chemical compound [K+].[O-]C(=O)C1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C1 CBPYOHALYYGNOE-UHFFFAOYSA-M 0.000 description 1
- XACWJIQLDLUFSR-UHFFFAOYSA-N pyrrolidine-1-carbonyl chloride Chemical compound ClC(=O)N1CCCC1 XACWJIQLDLUFSR-UHFFFAOYSA-N 0.000 description 1
- 239000003169 respiratory stimulant agent Substances 0.000 description 1
- 229940066293 respiratory stimulants Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 231100000816 toxic dose Toxicity 0.000 description 1
- 238000007056 transamidation reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/215—Radicals derived from nitrogen analogues of carbonic acid
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
Description
Verfahren zur Herstellung neuer N,N-Pentamethylen-harnstoffe
Gegenstand des vorliegenden Patentes bildet die Herstellung von neuen N,N-Pentamethylen-harnstof- fen der Formel I
EMI1.1
in welcher mindestens einer der Reste Rt und R2 Alkyl bedeutet, wobei R1 und R2 unter sich oder über ein Heteroatom zu einem Ring geschlossen sein können, und worin mindestens einer der Reste R3, R4 und R5 einen niederen Alkylrest darstellt. Diese neuen Harnstoffe sind wirksame Antihelminthica.
Es sind zwar schon Harnstoffe mit dem Ringsystem des Piperidins bekanntgeworden. So beschreiben Charles A. Weisel et al. in J. Am. Chem. Soc. 67, 1055-1056 (1945) den Umsatz von Harnstoff mit Piperidin zum Piperidyl-l -carbonsäureamid.
Durch das britische Patent Nr. 560680 sind bis Harnstoffe der Formel
EMI1.2
bekanntgeworden. In dieser Formel bedeuten R Alkylgruppen, X und Y sekundäre Aminogruppen, z. B. eine Dialkylamino- oder heterocyclische sekundäre Aminogruppe, und A einen Alkylenrest von 2-6 C-Atomen, welcher noch verschiedene Alkyl-, Alkoxy- oder Alkoxyalkylreste enthalten kann, Solche Harnstoffe dienen als atemanregende Mittel (vgl.
USA-Patent Nr. 2 398 283 und britisches Patent Nr. 560698 sowie die Arbeit von W. R. Boon über atemanregende Mittel in J. Chem. Soc. 1947, 307 bis 318).
In CA. 41, 3906d ist der N-(3-Chlor-phenyl)-N',N'- pentamethylen-harnstoff sowie das nichthalogenierte Derivat als das Pflanzenwachstum verhinderndes Mittel beschrieben.
Durch Walter Seibert ist der Umsatz eines Kondensationsproduktes von Harnstoff und Formaldehyd mit Piperidin bekanntgeworden. Das so erhaltene Piperidin-l-carboxamid hat keine abtötende Wirkung auf Würmer [Chem. Ber. 80, 494-502 (1947)]
Durch Ronald A. Henry et al. wurde in J. Am.
Chem. Soc., 71, 2297-2300 (1949) die Umsetzung von Phenyl-isocyanat, p-Tosyl-isocyanat und Naphthyl-isocyanat mit Piperidin und 2-Methyl-piperidin beschrieben. Die entsprechenden Piperidin- bzw.
2-Methyl-piperidin-l-carbonsäureamide wirken praktisch nicht auf Würmer ein;
Durch R. L. Rowiand et al. ist die Herstellung des Piperidin-1-carbonsäure-allylamides bekanrit- geworden. Dieses dient als Zwischenprodukt zur Herstellung von Quecksilberderivaten mit diuretischer Wirkung [J. Am. Chem. Soc. 73, 3691-3693 (1951)].
F. L. Scott et al. untersuchten die Reaktionen von Acylhydraziden, wobei sie u. a. auch das l-Thiocarbamyl-piperidin erhielten (Chemistry and Industry 1952, 107-108).
E. C. Taylor jun. beschrieb in J. Am. Chem. Soc.
74, 1651-1655 (1952) die Umamidierung des p-Nitrophenyl-harnstoffes mit Piperidin zum N-(p-Nitrophenyl)-N',N'-pentamethylen-harnstoff.
In der deutschen Patentschrift Nr. 923967 ist die Herstellung von N,N-Diäthyl-N',N'-pentamethylen- harnstoff beschrieben.
Ein eingehendes Studium der oben angeführten Verbindungen hat ergeben, dass keine derselben imstande ist, auf Würmer eine lähmende oder abtötende Wirkung in einer Konzentration auszuüben, die wesentlich unter der toxischen Dosis für Warmblüter liegt. Um so überraschender war es, zu finden, dass Harnstoffe der eingangs erwähnten Formel I imstande sind, schon in geringen Konzentrationen die Würmer zur Abtreibung zu bringen.
Das erfindungsgemässe Verfahren zur Herstellung der Verbindungen der Formel I ist dadurch gekennzeichnet, dass man ein reaktionsfähiges Derivat der Kohlensäure einerseits mit einem Amin der Formel II
EMI2.1
und anderseits mit einem Amin der Formel III
EMI2.2
in der Reihenfolge wahlweise umsetzt.
Man kann beispielsweise so vorgehen, dass man Phosgen mit einem Amin der Formel II bzw. einem Hydrochlorid desselben zur Reaktion bringt und das entstandene Piperidin-l-carbonsäure-chlorid mit einem Amin der Formel III weiter umsetzt. In inverser Reaktion kann man auch Phosgen zuerst mit einem Amin der Formel III und das entstandene Carbaminsäurechlorid mit einem Piperidin der Formel II umsetzen.
Es ist selbstverständlich auch möglich, z. B. einen Halogenkohlensäureester zu verwenden und diesen mit einem Piperidin der Formel II umzusetzen und den entstandenen N,N-Pentamethylen-carbaminsäure- ester mit einem Amin der Formel II zur Reaktion zu bringen oder in umgekehrter Reihenfolge den Halogenkohlensäureester mit einem Amin der Formel III reagieren zu lassen und den entstandenen Carbaminsäureester auf ein Piperidin der Formel II einwirken zu lassen.
Man kann z. B. auch ein Piperidin der Formel II mit Cyanwasserstoffsäure oder einer diese Säure liefernden Verbindung, z. B. Nitroharnstoff, umsetzen und den entstandenen Piperidyl-harnstoff mit einem Amin der Formel III oder vorzugsweise einem Säureadditionssalz eines solchen Amins umamidieren, wobei auch die umgekehrte Re aktion sfolge möglich ist.
Beispiel 1
Zu einer Lösung von 36,4 g 4-Methyl-piperidin in 100 cm3 absolutem Benzol wird eine Lösung von 25 g Diäthyl-carbaminsäure-chlorid, das durch Umsetzung von Diäthylamin mit Phosgen erhalten wurde, in 30 cm3 Benzol zugetropft. Nach Abklingen der Reaktion wird das Ganze unter Rühren 2 Stunden auf 80 C erwärmt. Nach dem Abkühlen wird das ausgefallene 4-Methyl-piperidin-hydrochlorid abgesaugt und das Filtrat im Vakuum eingeengt.
Der Rückstand wird im Vakuum destilliert. Man erhält so das unter 12 mm bei 124-125"C siedende 4 - Methyl - piperidin-l-carbonsäure-diäthylamid. Der neue Harnstoff löst sich leicht in üblichen organischen Lösungsmitteln, wenig aber in Wasser.
Man gelangt zu dem 4-Methyl-piperidin-1-car- bonsäure-diäthylamid auch sehr leicht, wenn man 4-Methyl-piperidin mit Phosgen umsetzt und das entstandene 4 - Methyl - piperidin-l-carbonsäure-chlorid mit Diäthylamin zur Reaktion bringt.
Setzt man analog 4-Methyl-piperidin mit dem durch Umsetzung von Pyrrolidin mit Phosgen erhaltenen Pyrrolidin-l-carbonsäure-chlorid um, so erhält man das 4-Methyl-piperidin- 1 -carbonsäure-N,N- tetramethylen-amid in guter Ausbeute.
Beispiel 2
Analog wie im Beispiel 1 beschrieben, erhält man aus 60 g 4-Methyl-piperidin und 32,3 g Dimethyl-carbaminsäure-chlorid, das durch Umsetzung von Dimethylamin mit Phosgen erhalten wurde, das 4-Methyl- piperidin-l-carbonsäure-dimethylamid in guter Ausbeute. Dieses siedet unter 12 mm Hg bei 115-116 C.
In gleicher Weise, wie für das 4-Methyl-piperidin beschrieben, kann man auch das 2,4-Dimethyl-piperidin und das 2,4,6-Trimethyl-piperidin mit Dimethylcarbaminsäure-chlorid, Diäthyl-carbaminsäure-chlorid oder Dipropyl-carbaminsäure-chlorid umsetzen.
Beispiel 3
Analog wie im Beispiel 1 beschrieben, erhält man aus 36,4 g 3-Methyl-piperidin und 25 g Diäthylcarbaminsäure-chlorid, 26 g des unter 12 mm Hg bei 123-1240 C siedenden 3-Methyl-piperidin- l-carbon- säure-diäthylamids.
Die genannte Substanz kann auch hergestellt werden, wenn man 3-Methyl-piperidin mit Chlorkohlensäure-phenylester und das erhaltene Urethan mit Diäthylamin ohne Lösungsmittel gemäss DB Patent Nr. 923967 umsetzt, oder wenn man 3-Methylpiperidin mit Nitroharnstoff zur Reaktion bringt und den erhaltenen Harnstoff mit Diäthylamin-hydrochlorid auf l90-210 C erhitzt.
Beispiel 4
Analog wie im Beispiel 2 beschrieben, erhält man aus 60 g 3-Methyl-piperidin und 32,3 g Dimethyl-carbaminsäure-chlorid 36 g des unter 12 mm Hg bei 114-115 C siedenden 3-Methyl-piperidin-lcarbonsäure-dimethylamids.
Setzt man 3-Methyl-piperidin mit Phosgen um und lässt auf das 3-Methyl-piperidin-l-carbonsäure- chlorid Piperidin oder Morpholin oder Pyrrolidin einwirken, so erhält man in guter Ausbeute die entsprechend konstituierten Harnstoffe.
Die neuen Harnstoffe können als aktive Komponenten in wurmtötenden Mitteln, gegebenenfalls zusammen mit einem andern, bekannten Vermizid und einem Trägerstoff verwendet werden. Als Trägerstoffe kommen flüssige, feste oder halbfeste Medien in Frage. Man kann die neuen Harnstoffe beispielsweise mit Hilfe von Emulgiermitteln in Wasser in feine Verteilung bringen und gegebenenfalls noch Geschmacksverbesserer zufügen, um einen Sirup zu erhalten. Die neuen Harnstoffe können aber auch in fester Form, z. B. als Tabletten oder Dragees, mit den entsprechenden Zusatzstoffen verpresst oder dragiert werden. Man kann sie auch in öliger Lösung in Kapseln abfüllen und so dem Warmblüter applizieren.
Process for the production of new N, N-pentamethylene ureas
The subject of the present patent is the production of new N, N-pentamethylene ureas of the formula I.
EMI1.1
in which at least one of the radicals Rt and R2 is alkyl, where R1 and R2 can be closed with one another or via a heteroatom to form a ring, and in which at least one of the radicals R3, R4 and R5 is a lower alkyl radical. These new ureas are effective antihelminthics.
It is true that ureas with the ring system of piperidine have already become known. For example, Charles A. Weisel et al. in J. Am. Chem. Soc. 67, 1055-1056 (1945) the conversion of urea with piperidine to piperidyl-l-carboxamide.
By British Patent No. 560680 bis are ureas of the formula
EMI1.2
known. In this formula, R are alkyl groups, X and Y are secondary amino groups, e.g. B. a dialkylamino or heterocyclic secondary amino group, and A is an alkylene radical of 2-6 carbon atoms, which can also contain various alkyl, alkoxy or alkoxyalkyl radicals, such ureas serve as breath-stimulating agents (cf.
U.S. Patent No. 2,398,283 and British Patent No. 560698 and the work by W. R. Boon on respiratory stimulants in J. Chem. Soc. 1947, 307 to 318).
In CA. 41, 3906d describes N- (3-chloro-phenyl) -N ', N'-pentamethylene urea and the non-halogenated derivative as an agent preventing plant growth.
Walter Seibert made the conversion of a condensation product of urea and formaldehyde with piperidine known. The piperidine-1-carboxamide obtained in this way has no killing effect on worms [Chem. Ber. 80, 494-502 (1947)]
By Ronald A. Henry et al. was reported in J. Am.
Chem. Soc., 71, 2297-2300 (1949) describes the reaction of phenyl isocyanate, p-tosyl isocyanate and naphthyl isocyanate with piperidine and 2-methylpiperidine. The corresponding piperidine resp.
2-methyl-piperidine-1-carboxamides have practically no effect on worms;
Rowiand, R. L. et al. the production of piperidine-1-carboxylic acid allylamide has become known. This serves as an intermediate product for the production of mercury derivatives with a diuretic effect [J. At the. Chem. Soc. 73, 3691-3693 (1951)].
F.L. Scott et al. studied the reactions of acylhydrazides, including i.a. a. also received the l-thiocarbamyl-piperidine (Chemistry and Industry 1952, 107-108).
E. C. Taylor jun. described in J. Am. Chem. Soc.
74, 1651-1655 (1952) the transamidation of p-nitrophenyl urea with piperidine to give N- (p-nitrophenyl) -N ', N'-pentamethylene urea.
The German patent specification No. 923967 describes the production of N, N-diethyl-N ', N'-pentamethylene urea.
A careful study of the above compounds has shown that none of them are capable of exerting a paralyzing or killing effect on worms in a concentration which is well below the toxic dose for warm-blooded animals. It was all the more surprising to find that ureas of the formula I mentioned at the beginning are able to induce an abortion in worms even in low concentrations.
The process according to the invention for the preparation of the compounds of the formula I is characterized in that a reactive derivative of carbonic acid is on the one hand with an amine of the formula II
EMI2.1
and on the other hand with an amine of the formula III
EMI2.2
optionally implemented in the order.
One can, for example, proceed in such a way that phosgene is reacted with an amine of the formula II or a hydrochloride thereof and the resulting piperidine-1-carboxylic acid chloride is reacted further with an amine of the formula III. In an inverse reaction, phosgene can also be reacted first with an amine of the formula III and the resulting carbamic acid chloride with a piperidine of the formula II.
It is of course also possible, for. B. to use a halocarbonate and to react this with a piperidine of the formula II and the resulting N, N-pentamethylene-carbamic acid ester to react with an amine of the formula II or, in reverse order, to react the halocarbonate with an amine of the formula III to let and to let the resulting carbamic acid ester act on a piperidine of the formula II.
You can z. B. also a piperidine of the formula II with hydrocyanic acid or a compound supplying this acid, e.g. B. nitrourea, and transamidate the resulting piperidyl urea with an amine of the formula III or preferably an acid addition salt of such an amine, the reverse reaction sequence is possible.
example 1
To a solution of 36.4 g of 4-methylpiperidine in 100 cm3 of absolute benzene, a solution of 25 g of diethyl carbamic acid chloride, which was obtained by reacting diethylamine with phosgene, in 30 cm3 of benzene is added dropwise. After the reaction has subsided, the whole is heated to 80 ° C. for 2 hours while stirring. After cooling, the precipitated 4-methylpiperidine hydrochloride is filtered off with suction and the filtrate is concentrated in vacuo.
The residue is distilled in vacuo. The 4-methyl-piperidine-1-carboxylic acid diethylamide boiling below 12 mm at 124-125 "C. is obtained in this way. The new urea dissolves easily in conventional organic solvents, but slightly in water.
The 4-methyl-piperidine-1-carboxylic acid diethylamide is also obtained very easily if 4-methyl-piperidine is reacted with phosgene and the 4-methyl-piperidine-1-carboxylic acid chloride is reacted with diethylamine .
If 4-methyl-piperidine is reacted analogously with the pyrrolidine-1-carboxylic acid chloride obtained by reacting pyrrolidine with phosgene, the 4-methyl-piperidine-1-carboxylic acid-N, N-tetramethylene amide is obtained in good yield .
Example 2
Analogously to that described in Example 1, 4-methylpiperidine-1-carboxylic acid dimethylamide is obtained from 60 g of 4-methylpiperidine and 32.3 g of dimethylcarbamic acid chloride, which was obtained by reacting dimethylamine with phosgene in good yield. This boils below 12 mm Hg at 115-116 C.
In the same way as described for 4-methylpiperidine, 2,4-dimethylpiperidine and 2,4,6-trimethylpiperidine can also be used with dimethylcarbamic acid chloride, diethylcarbamic acid chloride or dipropylcarbamic acid convert chloride.
Example 3
Analogously to that described in Example 1, from 36.4 g of 3-methyl-piperidine and 25 g of diethylcarbamic acid chloride, 26 g of 3-methyl-piperidine-1-carboxylic acid boiling below 12 mm Hg at 123-1240 ° C. are obtained diethylamide.
The substance mentioned can also be prepared if 3-methylpiperidine is reacted with phenyl chlorocarbonate and the urethane obtained with diethylamine without a solvent in accordance with DB Patent No. 923967, or if 3-methylpiperidine is reacted with nitrourea and the urea obtained is reacted heated to 190-210 ° C. with diethylamine hydrochloride.
Example 4
Analogously to that described in Example 2, 36 g of 3-methylpiperidine-lcarboxylic acid dimethylamide boiling below 12 mm Hg at 114-115 ° C. are obtained from 60 g of 3-methyl-piperidine and 32.3 g of dimethyl-carbamic acid chloride.
If 3-methyl-piperidine is reacted with phosgene and piperidine or morpholine or pyrrolidine is allowed to act on the 3-methyl-piperidine-1-carboxylic acid chloride, the correspondingly constituted ureas are obtained in good yield.
The new ureas can be used as active components in wormicides, optionally together with another known vermicide and a carrier. Liquid, solid or semi-solid media can be used as carriers. The new ureas can, for example, be finely dispersed in water with the aid of emulsifiers and, if necessary, flavor enhancers can be added in order to obtain a syrup. The new ureas can also be in solid form, e.g. B. as tablets or coated tablets, pressed or coated with the appropriate additives. They can also be filled into capsules in an oily solution and applied to warm-blooded animals.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH6283158A CH367171A (en) | 1958-08-12 | 1958-08-12 | Process for the production of new N, N-pentamethylene ureas |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH6283158A CH367171A (en) | 1958-08-12 | 1958-08-12 | Process for the production of new N, N-pentamethylene ureas |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH367171A true CH367171A (en) | 1963-02-15 |
Family
ID=4524553
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH6283158A CH367171A (en) | 1958-08-12 | 1958-08-12 | Process for the production of new N, N-pentamethylene ureas |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH367171A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2405938A1 (en) * | 1976-12-17 | 1979-05-11 | Rohm & Haas | INSECTIVE COMPOUNDS, ESPECIALLY FOR ARTHROPODS, AND THEIR APPLICATION METHOD |
| US4357471A (en) | 1976-12-17 | 1982-11-02 | Rohm And Haas Company | Azaspiro compounds |
| US4374991A (en) | 1976-12-17 | 1983-02-22 | Rohm And Haas Company | 2,6-Dimethylpiperidinyl-N-carbobutoxymethyl urea |
| US4400512A (en) * | 1976-12-17 | 1983-08-23 | Rohm And Haas Company | Azaspiro compounds |
| US4405630A (en) * | 1980-12-29 | 1983-09-20 | Rohm And Haas Company | Arthropod repellent compositions and methods |
| EP0094350A3 (en) * | 1982-05-10 | 1987-04-15 | Ciba-Geigy Ag | Process for producing 1-diorganocarbamoyl-polyalkyl piperidines |
| EP0613892A1 (en) * | 1993-01-22 | 1994-09-07 | DSM Chemie Linz GmbH | Cyclization and process for the preparation of N-cyclic and N,N'-dicylic ureas |
-
1958
- 1958-08-12 CH CH6283158A patent/CH367171A/en unknown
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2405938A1 (en) * | 1976-12-17 | 1979-05-11 | Rohm & Haas | INSECTIVE COMPOUNDS, ESPECIALLY FOR ARTHROPODS, AND THEIR APPLICATION METHOD |
| US4357471A (en) | 1976-12-17 | 1982-11-02 | Rohm And Haas Company | Azaspiro compounds |
| US4374991A (en) | 1976-12-17 | 1983-02-22 | Rohm And Haas Company | 2,6-Dimethylpiperidinyl-N-carbobutoxymethyl urea |
| US4400512A (en) * | 1976-12-17 | 1983-08-23 | Rohm And Haas Company | Azaspiro compounds |
| US4405630A (en) * | 1980-12-29 | 1983-09-20 | Rohm And Haas Company | Arthropod repellent compositions and methods |
| EP0094350A3 (en) * | 1982-05-10 | 1987-04-15 | Ciba-Geigy Ag | Process for producing 1-diorganocarbamoyl-polyalkyl piperidines |
| US4788283A (en) * | 1982-05-10 | 1988-11-29 | Ciba-Geigy Corporation | 1-Diorganocarbamoyl-polyalkylpiperidines |
| EP0613892A1 (en) * | 1993-01-22 | 1994-09-07 | DSM Chemie Linz GmbH | Cyclization and process for the preparation of N-cyclic and N,N'-dicylic ureas |
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