CH259961A - Process for making a diamine. - Google Patents
Process for making a diamine.Info
- Publication number
- CH259961A CH259961A CH259961DA CH259961A CH 259961 A CH259961 A CH 259961A CH 259961D A CH259961D A CH 259961DA CH 259961 A CH259961 A CH 259961A
- Authority
- CH
- Switzerland
- Prior art keywords
- phenyl
- oxy
- methyl
- diamine
- formula
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 7
- 150000004985 diamines Chemical class 0.000 title claims description 5
- 239000003054 catalyst Substances 0.000 claims description 4
- 239000013078 crystal Substances 0.000 claims description 4
- 230000002378 acidificating effect Effects 0.000 claims description 3
- 230000007062 hydrolysis Effects 0.000 claims description 3
- 238000006460 hydrolysis reaction Methods 0.000 claims description 3
- 230000003301 hydrolyzing effect Effects 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 238000005984 hydrogenation reaction Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 229910052751 metal Inorganic materials 0.000 claims description 2
- 239000002184 metal Substances 0.000 claims description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical group [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WZELXJBMMZFDDU-UHFFFAOYSA-N Imidazol-2-one Chemical class O=C1N=CC=N1 WZELXJBMMZFDDU-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- CAAMSDWKXXPUJR-UHFFFAOYSA-N 3,5-dihydro-4H-imidazol-4-one Chemical compound O=C1CNC=N1 CAAMSDWKXXPUJR-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- LRNGDEHBVKSHOV-UHFFFAOYSA-N 1-cyclohexylbutane-2,3-diamine Chemical compound CC(N)C(N)CC1CCCCC1 LRNGDEHBVKSHOV-UHFFFAOYSA-N 0.000 description 1
- DZXPVTRPJUYHRK-UHFFFAOYSA-N 1-cyclohexylpropane-1,2-diamine Chemical compound CC(N)C(N)C1CCCCC1 DZXPVTRPJUYHRK-UHFFFAOYSA-N 0.000 description 1
- IEOVAZVJCNUJPI-UHFFFAOYSA-N 1-phenylbutane-2,3-diamine Chemical compound CC(N)C(N)CC1=CC=CC=C1 IEOVAZVJCNUJPI-UHFFFAOYSA-N 0.000 description 1
- ISIJGZLHZALNDU-UHFFFAOYSA-N 2-n-methyl-1-phenylpropane-1,2-diamine Chemical compound CNC(C)C(N)C1=CC=CC=C1 ISIJGZLHZALNDU-UHFFFAOYSA-N 0.000 description 1
- CXFFQOZYXJHZNJ-UHFFFAOYSA-N 3-phenylpropane-1,2-diamine Chemical compound NCC(N)CC1=CC=CC=C1 CXFFQOZYXJHZNJ-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- -1 alkali metal cyanate Chemical class 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical class O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Verfahren zur Herstellung eines Diamins. Es wurde gefunden, dass Diamine der Formel
EMI0001.0002
in welcher R H oder OH, RI H oder Methyl, Q Phenyl oder einen hydrierten Phenylkern und n Null oder 1 bedeuten, wobei mindestens ein n 1 sein soll, wertvolle therapeutische Eigenschaften aufweisen. Die neuen Verbin dungen besitzen bei sehr niedriger Toxität ausgeprägte Wirkungen auf den Blutdruck.
Die Herstellung der Verbindungen gemäss Formel I kann sowohl durch katalytische Re duktion als auch durch katalytische Hydrie- rung der Imidazolone der Formel II oder deren acylierten Derivaten und durch Hydro- lysieren der so erhaltenen Imidazolidone der Formel III erfolgen, wobei die Hydro- lysierung entweder unter sauren oder alkali- sehen Bedingungen durchführbar ist.
Zur Er läuterung der Reaktionen diene folgendes Re aktionsschema, in welchem R., R.1 und n die gleiche Bedeutung wie oben haben:
EMI0001.0023
Auf diese Weise lassen sich beispielsweise die folgenden Verbindungen der Formel I leicht herstellen: 1-(3',4'-Dioxy-phenyl)-N'-methyl-äthylen- diamin.
1- (3'- Oxy - phenyl) - N2 - methyl - äthylen- diamin.
1-Phenyl-N'-methyl-1,2-propandiamin. 1-(p-Oxy-phenyl)-1,2-propandiamin. 1-Cyclohexyl-1,2-propandiamin. 3-Phenyl-1,2-propandiamin. 3-Cyclohexyl-1,2-propandiainin. 3-Phenyl-3-oxy-1,2-propandiamin. 3-Cyclohexyl-3-oxy-1,2-propandiamin. 1-Phenyl-2,3-butandiamin. 1-Cyclohexyl-2,3-butandiamin. 1-Phenyl-l-oxy-2,3-biitandiamin, und die Salze dieser Verbindungen mit . Säuren, wie beispielsweise die Dihydrochloride oder Sulfate.
Die Imidazolone der Formel II, in welcher das n der (CO)" -Gruppe Null bedeutet, kön nen durch Umsetzen von Aryl-a-aminoalkyl- ketonen oder Aryl=a-alkylaminoalkyl-ketonen mit einem Alkalimetallcyanat leicht hergestellt werden, wobei . der Phenylkern des Ketons substituiert oder unsnbstituiert sein kann.
Die Imidazolöne der Formel II, die eine (CO),; Bindung enthalten, in welcher n 1 bedeutet, können nach dem von Dusehinsky und Dolan im Journal of the American Chemical Society 67 (1945), S. 2079, und 68 (1946), S. 2350, beschriebenen Verfahren gewonnen werden.
Gegenstand des vorliegenden Patentes ist ein Verfahren zur Herstelhzng eines Diamins, welches dadurch gekennzeichnet ist, dass 1-Methyl-4-(3'-oxy-phenyl)-2-imidazolon zu 1-Methyl-(3'-oxy-phenyl)-2-imidazolidon hy driert und dieses dann zu 1-(3'-Oxy-phenyl)- N'-methyl-äthylendiamin hydrolysiert wird. Als Hydrierungskatalysator wird zweclmässi- gerweise ein Metall der Platingruppe verwen det.
Die Hydrolyse kann mit Vorteil durch Einwirkung eines sauren Hydrolysierungs- mittels, wie z. B. Salzsäure, bewirkt werden.
Die neue Verbindung, deren Dihydro- chlorid aus farblosen Kristallen vom Schmelz punkt 199 bis 200 C besteht, soll als Arznei mittel verwendet werden.
Beispiel: Eine Lösung von 10,08 g a-Methylamino- m-oxy-acetophenon-hydrochlorid und 8,1 g Kaliumcyanat in 200 cm' Wasser wird wäh rend 20 Minuten bei 90 bis 100 C erhitzt. Nach wenigen Minuten beginnt die Kristal lisation des Imidazolons. Durch Abkühlen und Ansäuern mit 10 cm3 5-n-Salzsäure erhält. man rohes 1-Methyl-4-(3'-oxy-phenyl)-2-imid- azolon vom Schmelzpunkt 250 bis 253 C.
Die Verbindung wird aus Äthanol umkristalli siert; Schmelzpunkt 252 bis 254 C.
Eine Mischung von 12,6 g des erhaltenen Imidazolons, 5 g eines 3,5 j igen Palladium- kohlekatalysators und 70 cm' Essigsäure wird bei einem Druck von 31/2 Atü und einer Temperatur von ungefähr 65 C während 2 Stunden hydriert. Die vom Katalysator ab filtrierte Lösung wird zum Sirup konzentriert. Nach Zugabe von 40 cm' Wasser scheidet sich das 1-Methyl-4-(3'-oxy-phenyl)-2-imiclazolidon in Form von Kristallen ab; Schmelzpunkt 162 bis 164 C.
Nach dem Umkristallisieren aus dem 7,5faehen Volumen Wasser schmilzt die Verbindung bei 163 bis 165 C.
10,7 g 1-',vIethyl-4-(3'oxy-phenyl)-2-imid- azolidon werden mit 300 ein- konzentrierter Salzsäure und 30 cm' Wasser während 5 Stunden am Rückflusskühler gekocht. Die Lösung wird im Vakuum eingedampft und der entstehende Rückstand aus 75 cni' Äthanol kristallisiert.
Die abgeschiedenen Kristalle von 1-(3'-Oxy-phenyl)-N=-methyl-äthylen- diamin-dihydroehlorid vom Sehinelzpunkt <B>197</B> bis 199 C können durch Lösen in dem 1.Ofachen Volumen Methanol unter Zugabe des 30fachen Vohunens Äther ohne nennens werten Verlust umkristallisiert werden, wo durch der Schmelzpunkt auf 199 bis 200 C gesteigert wird. Aus dem Dihydroehlorid kann die Base mittels Alkalien (z.
B. wäss riger Sodalösimg) in Freiheit gesetzt werden; sie ist in überschüssiger Alkalilauge löslich.
Process for making a diamine. It has been found that diamines have the formula
EMI0001.0002
in which R is H or OH, RI is H or methyl, Q is phenyl or a hydrogenated phenyl nucleus and n is zero or 1, at least one n being 1, have valuable therapeutic properties. The new compounds have pronounced effects on blood pressure with very low toxicity.
The compounds according to formula I can be prepared either by catalytic reduction or by catalytic hydrogenation of the imidazolones of the formula II or their acylated derivatives and by hydrolyzing the imidazolidones of the formula III thus obtained, the hydrolysis either being below acidic or alkaline see conditions is feasible.
The following reaction scheme is used to explain the reactions, in which R., R. 1 and n have the same meaning as above:
EMI0001.0023
In this way, for example, the following compounds of the formula I can easily be prepared: 1- (3 ', 4'-dioxy-phenyl) -N'-methyl-ethylene diamine.
1- (3'-oxy-phenyl) -N2-methyl-ethylene diamine.
1-phenyl-N'-methyl-1,2-propanediamine. 1- (p-Oxy-phenyl) -1,2-propanediamine. 1-cyclohexyl-1,2-propanediamine. 3-phenyl-1,2-propanediamine. 3-Cyclohexyl-1,2-propanediainine. 3-phenyl-3-oxy-1,2-propanediamine. 3-cyclohexyl-3-oxy-1,2-propanediamine. 1-phenyl-2,3-butanediamine. 1-Cyclohexyl-2,3-butanediamine. 1-phenyl-l-oxy-2,3-biitandiamine, and the salts of these compounds with. Acids, such as the dihydrochlorides or sulfates.
The imidazolones of the formula II, in which the n of the (CO) "group denotes zero, can easily be prepared by reacting aryl-a-aminoalkyl ketones or aryl = a-alkylaminoalkyl ketones with an alkali metal cyanate, the Phenyl nucleus of the ketone can be substituted or unsnstituted.
The imidazolones of formula II, the one (CO) ,; Bond in which n is 1 can be obtained by the method described by Dusehinsky and Dolan in Journal of the American Chemical Society 67 (1945), p. 2079, and 68 (1946), p. 2350.
The subject of the present patent is a process for the production of a diamine, which is characterized in that 1-methyl-4- (3'-oxy-phenyl) -2-imidazolone to 1-methyl- (3'-oxy-phenyl) - 2-imidazolidone hydrates and this is then hydrolyzed to 1- (3'-oxy-phenyl) - N'-methyl-ethylenediamine. A platinum group metal is used as the hydrogenation catalyst.
The hydrolysis can be carried out with advantage by the action of an acidic hydrolyzing agent, such as. B. hydrochloric acid.
The new compound, whose dihydrochloride consists of colorless crystals with a melting point of 199 to 200 C, is intended to be used as a medicinal product.
Example: A solution of 10.08 g of a-methylamino-m-oxy-acetophenone hydrochloride and 8.1 g of potassium cyanate in 200 cm of water is heated at 90 to 100 ° C. for 20 minutes. After a few minutes, the imidazolone starts to crystallize. Obtained by cooling and acidifying with 10 cm3 of 5N hydrochloric acid. crude 1-methyl-4- (3'-oxy-phenyl) -2-imid-azolone with a melting point of 250 to 253 C.
The compound is recrystallized from ethanol; Melting point 252 to 254 C.
A mixture of 12.6 g of the imidazolone obtained, 5 g of a 3.5% palladium-carbon catalyst and 70 cm acetic acid is hydrogenated at a pressure of 3 1/2 atmospheres and a temperature of approximately 65 ° C. for 2 hours. The solution filtered off from the catalyst is concentrated to a syrup. After adding 40 cm 'of water, the 1-methyl-4- (3'-oxy-phenyl) -2-imiclazolidone separates out in the form of crystals; Melting point 162 to 164 C.
After recrystallization from 7.5 times the volume of water, the compound melts at 163 to 165 C.
10.7 g of 1 - ', vIethyl-4- (3'oxyphenyl) -2-imidazolidone are boiled with 300 concentrated hydrochloric acid and 30 cm' of water for 5 hours on the reflux condenser. The solution is evaporated in vacuo and the resulting residue is crystallized from 75 cni 'of ethanol.
The deposited crystals of 1- (3'-oxy-phenyl) -N = -methyl-ethylene-diamine-dihydrochloride with a melting point <B> 197 </B> to 199 C can be dissolved by dissolving in the 1.Ofold volume of methanol with addition 30-fold Vohunens ether can be recrystallized without significant loss, where the melting point is increased to 199 to 200 ° C. The base can be extracted from the dihydrochloride by means of alkalis (e.g.
B. aqueous Sodalösimg) be set free; it is soluble in excess alkali.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US259961XA | 1946-12-26 | 1946-12-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH259961A true CH259961A (en) | 1949-02-15 |
Family
ID=21829242
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH259961D CH259961A (en) | 1946-12-26 | 1947-12-11 | Process for making a diamine. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH259961A (en) |
-
1947
- 1947-12-11 CH CH259961D patent/CH259961A/en unknown
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