PL135686B2 - Process for preparing novel derivatives of n1 upwards,-n2 upwards-dialkyl-1-phenylethylenodiamine - Google Patents

Process for preparing novel derivatives of n1 upwards,-n2 upwards-dialkyl-1-phenylethylenodiamine Download PDF

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PL135686B2
PL135686B2 PL23997882A PL23997882A PL135686B2 PL 135686 B2 PL135686 B2 PL 135686B2 PL 23997882 A PL23997882 A PL 23997882A PL 23997882 A PL23997882 A PL 23997882A PL 135686 B2 PL135686 B2 PL 135686B2
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upwards
phenylethylenediamine
dialkyl
alkyl
general formula
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PL23997882A
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PL239978A2 (en
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Tadeusz Tkaczynski
Danuta Tkaczynska
Zdzislaw Winiarski
Zdzislaw Kleinrok
Iwona Zebrowskalupina
Marian Wielosz
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Akad Medyczna
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Przedmiotem wynalazku jest sposób otrzymywania nowych pochodnych NI,N2-dialkilo-l-fe- nyloetylenodiaminy o ogólnym wzorze I, w którym R oznacza atom wodoru, chlorowca, grupe alkilowa lub trifluorometylowa, R' i R" oznaczaja grupe alkilowa, cykloalkilowa lub aryloalkilowa.Z grupy pochodnych 1-fenyloetylenodiaminy znane sa i stosowane jako pólprodukty do syntezy srodków dzialajacych na osrodkowy uklad nerwowy i uklad krazenia, pochodne N^alkilo- 1-fenyloetylenodiaminy. Wymienione, znane pochodne 1-fenyloetylenodiaminy otrzymuje sie mie¬ dzy innymi przez hydrolize wodorotlenkiem potasowym N^alkilo-N^acetylo- 1-fenyloetylenodi¬ aminy w srodowisku alkoholu benzylowego. (Funke i Kornmann. Buli. Soc. Chim. Fr. 1949, 245).Z opisów patentowych RFN nry 2 633 679 i 2 733 698 znany jest sposób otrzymywania wymienio¬ nych pochodnych polegajacy na redukcji pochodnych nitrylu kwasu a-aminofenylooctowego wodorkiem litowo-glinowym. Wspomniec jeszcze nalezy o sposobach wzmiankowanych w opisie patentowym RFN nr 2 235 328, polegajacy na wodorowaniu pochodnych nitrylu kwasu a-amino¬ fenylooctowego.Bedace przedmiotem wynalazku, nowe zwiazki o podanym wzorze ogólnym, otrzymuje sie na drodze redukcyjnego alkilowania pochodnych 1-fenyloetylenodiaminy, to jest zwiazku o wzorze ogólnym II, w którym symbole R i R' maja wyzej podane znaczenie, stosujac jako czynniki alkilujace aldehydy lub ketony, a jako czynnik redukujacy wodór wobec katalizatora, korzystnie niklu Raney'a lub kwas mrówkowy.Wedlug wynalazku, N^alkilo-1-fenyloetylenodiamine, to jest zwiazek o wzorze ogólnym II, kondensuje sie z aldehydem lub ketonem w srodowisku rozpuszczalnika organicznego, korzystnie benzenu lub alkoholu metylowego, w temperaturze 0-150°C, nastepnie powstala zasade Schiffa bez wyodrebniania lub po jej wyodrebnieniu poddaje sie redukcji wodorem wobec katalizatora, korzy¬ stnie niklu Raney'a lub kwasem mrówkowym, po czym po odsaczeniu katalizatora i oddestylowa¬ niu rozpuszczalnikaprodukt wyodrebnia sie przez destylacje, korzystnie pod zmniejszonym cisnieniem lub wydziela w postaci soli z kwasami nieorganicznymi lub organicznymi, korzystnie z kwasem solnym i oczyszcza przez krystalizacje, korzystnie z alkoholu alifatycznego.2 135686 Stanowiacy substral w sposobie wedlug wynalazku, zwiazek o wzorze ogólnym II jest zwia¬ zkiem znanym, otrzymywanym najczesciej przez redukcje pochodnych nitrylu kwasu N-alkilo-a- aminofenylooctowego lub przez hydrolize pochodnych l,2-dialkilo-5-fenyloimidazoliny. Nowe zwiazki otrzymane sposobem wedlug wynalazku, wykazuja dzialanie przeciwdrgawkowe. Zwiazki te moga byc takze surowcami do wytwarzania innych zwiazków o potencjalnym dzialaniu farmakologicznym.Przyklad I. W kolbie o pojemnosci 250 cm3 umieszcza sie 45 g (0,2 mola) N^benzylo-1-1 e- nyloetylenodiaminy i 50 cm3 alkoholu metylowego. Do powstalej mieszaniny wkrapla sie 9g (0,2 mola) aldehydu octowego i calosc ogrzewa na lazni wodnej w ciagu 2 godzin. Otrzymana mieszanine (zawierajaca zasade Schiffa) przenosi sie do autoklawu o pojemnosci 320 cm3, dodaje 1 g niklu Raney'a, zaladowuje autoklaw wodorem do cisnienia 40atm., i ogrzewa w temperaturze 130 ± 5° przez 2 godziny. Cisnienie poczatkowo wzrasta do okolo 50 atm. a nastepnie powoli opada do okolo 20 atm. (po oziebieniu). W reakcji zuzywa sie okolo 4,5 litra wodoru. Po zdekantowaniu znad niklu Raney'a metanolowego roztworu produktu i oddestylowaniu metanolu do pozostalosci dodaje sie 50 cm3 stezonego kwasu solnego i powstala mieszanine pozostawia na 20 godzin w lodówce. Wydzielone krysztaly odsacza sie i przekrystalizowuje z metanolu (1:2). Otrzymuje sie 38 g (58%) dwuchlorowodorku N^benzylo-N^tylo-1-fenyloetylenodiaminy o temperaturze topnienia 233-5°C.Analiza dla wzoru Cn^^-2HC1 (m.cz. 327,3) obliczono: 8,55% N znaleziono: 8,53% N obliczono: 21,7% Cl znaleziono: 22,1% Cl Przyklad II. Postepujac analogicznie jak w przykladzie I przez zastapienie 9g aldehydu octowego 12 g (0,2 mola) acetonu otrzymano 54 g dwuchlorowodorku o tempraturze topnienia 232-4°C.Przyklad III. Postepujac analogicznie jak w przykladzie I, zastosowano zamiast N'-benzy- lo-1-fenyloetylenodiaminy, N'-metylo-l-/4-chlorofenylo/-etylenodiamine i zamiast aldehydu octowego, aldehyd benzoesowy. Otrzymano 42 g dwuchlorowodorku N'-metylo-N2-benzy- lo-l-/4-chlorofenylo/-etylenodiaminy o temperaturze topnienia 232-5°C.Analiza dla wzoru Ci6Hi9ClN2 • 2HC1 (m.cz. 347,7) obliczono: 55,26% C znaleziono: 55,57% C 6,09%H 6,26% H 8,06%N 8,00% N Zastrzezenie patentowe Sposób otrzymywania nowych pochodnych N^N^dialkilo-l-fenyloetylenodiaminy o wzorze ogólnym I, w którym R oznacza atom wodoru, chlorowca, grupe alkilowa lub trifluorometylowa, R' i R" oznaczaja grupe alkilowa, cykloalkilowa lub aryloalkilowa, znamienny tym, ze stanowiacy pochodna 1-fenyloetylenodiaminy zwiazek o wzorze ogólnym II, w którym symbole R i R' maja wyzej podane znaczenie, kondensuje sie z aldehydem lub ketonem, korzystnie w srodowisku rozpuszczalnika organicznego, zwlaszcza benzenu lub alkoholu metylowego w temperaturze 0-150°C, nastepnie powstala zasade Schiffa bez wyodrebniania lub pojej wyodrebnieniu poddaje sie redukcji wodorem wobec katalizatora, korzystnie niklu Raney'a lub kwasem mrówkowym, po czym produkt wyodrebnia sie przez destylacje pod zmniejszonym cisnieniem lub wydziela w postaci soli.135 686 R-NH-CH-CH2-NH-R" O R'-NH-CH-CHrNH2 PLThe subject of the invention is a process for the preparation of new NI, N2-dialkyl-1-phenylethylenediamine derivatives of general formula I, in which R represents a hydrogen atom, a halogen atom, an alkyl or trifluoromethyl group, and R 'and R "represent an alkyl, cycloalkyl or arylalkyl group. From the group of 1-phenylethylenediamine derivatives, the N-alkyl-1-phenylethylenediamine derivatives are known and used as intermediates for the synthesis of agents acting on the central nervous system and the circulatory system. N-alkyl-N-acetyl-1-phenylethylenediamine in the environment of benzyl alcohol (Funke and Kornmann. Bull. Soc. Chim. Fr. 1949, 245). From German patents Nos. 2 633 679 and 2 733 698 it is known a method of obtaining the above-mentioned derivatives by reducing the α-aminophenylacetic acid nitrile derivatives with lithium aluminum hydride. It is also worth mentioning the methods mentioned in the patent specification. Germany No. 2,235,328, which is based on the hydrogenation of α-amino-phenylacetic acid nitrile derivatives. The novel compounds of the general formula given for the present invention are obtained by reductive alkylation of 1-phenylethylenediamine derivatives, i.e. a compound of general formula II, in which the symbols R and R 'have the above meanings when using aldehydes or ketones as alkylating agents and hydrogen as reducing agent with respect to a catalyst, preferably Raney nickel or formic acid. According to the invention, N- alkyl-1-phenylethylenediamine, i.e. a compound with of general formula II, is condensed with an aldehyde or ketone in an organic solvent environment, preferably benzene or methyl alcohol, at a temperature of 0-150 ° C, then the resulting Schiff's base is obtained without isolation or, after its isolation, is reduced with hydrogen in the presence of a catalyst, preferably nickel Raney or formic acid, and then, after filtering off the catalyst and distilling off the solvent, the product is isolated by de styling, preferably under reduced pressure or salted with inorganic or organic acids, preferably hydrochloric acid, and purified by crystallization, preferably from an aliphatic alcohol.2 135686 The compound of the general formula II is a known compound in the process of the invention. , usually obtained by reduction of N-alkyl-α-aminophenylacetic acid nitrile derivatives or by hydrolysis of 1,2-dialkyl-5-phenylimidazoline derivatives. The new compounds obtained with the method according to the invention show an anticonvulsant effect. These compounds may also be raw materials for the production of other compounds with a potential pharmacological action. Example 1. In a 250 cm3 flask is placed 45 g (0.2 mol) of N- benzyl-1-1 e-ethylenediamine and 50 cm3 of methyl alcohol. 9 g (0.2 mol) of acetaldehyde were added dropwise to the mixture and the mixture was heated in a water bath for 2 hours. The mixture obtained (containing Schiff's base) is transferred to an autoclave with a capacity of 320 cm3, 1 g of Raney nickel is added, the autoclave is charged with hydrogen to a pressure of 40 atm and heated at 130 ± 5 ° for 2 hours. The pressure initially increases to about 50 atm. and then slowly drops to about 20 atm. (after cooling down). About 4.5 liters of hydrogen are consumed in the reaction. After the methanolic product solution has been decanted from the Raney nickel and the methanol has been distilled off, 50 cm 3 of concentrated hydrochloric acid are added to the residue and the resulting mixture is left for 20 hours in the refrigerator. The separated crystals are filtered off and recrystallized from methanol (1: 2). There are obtained 38 g (58%) of N, 2-benzyl-N-yl-1-phenylethylenediamine dihydrochloride with a melting point of 233-5 ° C. Analysis for the formula Cn2- 2HCl (MW 327.3) calculated: 8, 55% N found: 8.53% N calculated: 21.7% Cl found: 22.1% Cl Example II. Proceeding analogously to Example 1, by substituting 9 g of acetaldehyde with 12 g (0.2 mol) of acetone, 54 g of dihydrochloride with a melting point of 232-4 ° C was obtained. Example III. In an analogous manner to Example I, N'-benzyl-1-phenylethylenediamine, N'-methyl-1- (4-chlorophenyl) -ethylenediamine was used instead of acetaldehyde, benzaldehyde. 42 g of N'-methyl-N2-benzyl-1- (4-chlorophenyl) -ethylenediamine dihydrochloride with a melting point of 232-5 ° C were obtained. Analysis for the formula C16Hi9ClN2.2HCl (MW 347.7) was calculated: 55.26% C found: 55.57% C 6.09% H 6.26% H 8.06% N 8.00% N Patent claim Method for the preparation of new N2N4 dialkyl-1-phenylethylenediamine derivatives with the general formula I, in which R is hydrogen, halogen, alkyl or trifluoromethyl, R 'and R "are alkyl, cycloalkyl or arylalkyl groups, characterized in that the 1-phenylethylenediamine derivative is a compound of general formula II, in which the symbols R and R They have the meaning given above, they are condensed with an aldehyde or a ketone, preferably in an organic solvent environment, especially benzene or methyl alcohol, at a temperature of 0-150 ° C, then the resulting Schiff's base without isolation or its isolation is reduced with hydrogen in the presence of a catalyst, preferably nickel Raney or formic acid, then the product v It is isolated by distillation under reduced pressure or is separated as a salt. 135 686 R-NH-CH-CH2-NH-R "O R'-NH-CH-CHrNH2 PL

Claims (1)

1. Zastrzezenie patentowe Sposób otrzymywania nowych pochodnych N^N^dialkilo-l-fenyloetylenodiaminy o wzorze ogólnym I, w którym R oznacza atom wodoru, chlorowca, grupe alkilowa lub trifluorometylowa, R' i R" oznaczaja grupe alkilowa, cykloalkilowa lub aryloalkilowa, znamienny tym, ze stanowiacy pochodna 1-fenyloetylenodiaminy zwiazek o wzorze ogólnym II, w którym symbole R i R' maja wyzej podane znaczenie, kondensuje sie z aldehydem lub ketonem, korzystnie w srodowisku rozpuszczalnika organicznego, zwlaszcza benzenu lub alkoholu metylowego w temperaturze 0-150°C, nastepnie powstala zasade Schiffa bez wyodrebniania lub pojej wyodrebnieniu poddaje sie redukcji wodorem wobec katalizatora, korzystnie niklu Raney'a lub kwasem mrówkowym, po czym produkt wyodrebnia sie przez destylacje pod zmniejszonym cisnieniem lub wydziela w postaci soli.135 686 R-NH-CH-CH2-NH-R" O R'-NH-CH-CHrNH2 PLClaim 1. A method for the preparation of new N, N-, dialkyl-1-phenylethylenediamine derivatives of general formula I, in which R represents a hydrogen atom, a halogen atom, an alkyl or trifluoromethyl group, R 'and R "represent an alkyl, cycloalkyl or arylalkyl group, characterized by that a compound of the general formula II, which is a derivative of 1-phenylethylenediamine, in which the symbols R and R 'have the meaning given above, is condensed with an aldehyde or ketone, preferably in an organic solvent environment, especially benzene or methyl alcohol at a temperature of 0-150 ° C C, the resulting Schiff's base is then reduced without isolation or its isolation is reduced with hydrogen in the presence of a catalyst, preferably Raney nickel or formic acid, and the product is isolated by distillation under reduced pressure or is separated as a salt. 135 686 R-NH-CH -CH2-NH-R "O R'-NH-CH-CHrNH2 PL
PL23997882A 1982-12-31 1982-12-31 Process for preparing novel derivatives of n1 upwards,-n2 upwards-dialkyl-1-phenylethylenodiamine PL135686B2 (en)

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