DE1041502B - Process for the preparation of a new hydantoin compound - Google Patents

Process for the preparation of a new hydantoin compound

Info

Publication number
DE1041502B
DE1041502B DER20915A DER0020915A DE1041502B DE 1041502 B DE1041502 B DE 1041502B DE R20915 A DER20915 A DE R20915A DE R0020915 A DER0020915 A DE R0020915A DE 1041502 B DE1041502 B DE 1041502B
Authority
DE
Germany
Prior art keywords
hydantoin
phenyl
tert
butyl
preparation
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
Application number
DER20915A
Other languages
German (de)
Inventor
Dr Albrecht Heymons
Dr Walther Persch
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Honeywell Riedel de Haen AG
Original Assignee
Riedel de Haen AG
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Riedel de Haen AG filed Critical Riedel de Haen AG
Priority to DER20915A priority Critical patent/DE1041502B/en
Publication of DE1041502B publication Critical patent/DE1041502B/en
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D233/72—Two oxygen atoms, e.g. hydantoin
    • C07D233/74—Two oxygen atoms, e.g. hydantoin with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to other ring members

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Description

Verfahren zur Herstellung einer neuen Hydantoinverbindung Es wurde gefunden, daß das bisher nicht bekannte 5-Phenyl-5-tert.-butyl-hydantoin bei geringer Toxizität eine ausgeprägte antikonvulsive Wirkung besitzt. In der nachstehenden Tabelle wird die Wirkung des 5-Phenyl-5-tert.-butyl-hydantoin mit der Wirkung von 5-Phenyl-5-isobutyl-hydantoin, 5-Phenyl-5-n-butyl-hydantoin 5-Phenyl-5-(1-methyl-propyl)-hydantoin, 5-Phenyl-5-isopropyl-hydantoin, 5-Phenyl-5-n-propyl-hydantoin, 5,5-Diphenyl-hydantoin und 5-Methyl-5-tert.-butyl-hydantoin nach der Prüfungsmethodik, wie sie in der "Arzneimittel-Forschung" 1955, S. 357, beschrieben wird, verglichen.Process for the preparation of a new hydantoin compound It has been found that the previously unknown 5-phenyl-5-tert-butyl-hydantoin at low Toxicity has a pronounced anticonvulsant effect. In the following Table shows the effect of 5-phenyl-5-tert.-butyl-hydantoin with the effect of 5-phenyl-5-isobutyl-hydantoin, 5-phenyl-5-n-butyl-hydantoin, 5-phenyl-5- (1-methyl-propyl) -hydantoin, 5-phenyl-5-isopropyl-hydantoin, 5-phenyl-5-n-propyl-hydantoin, 5,5-diphenyl-hydantoin and 5-methyl-5-tert.-butyl-hydantoin according to the test methodology as used in "drug research" 1955, p. 357, is compared.

Alle Verbindungen sind an der Ratte bei oraler Applikation geprüft worden. In jedem Falle wurde die Zeit für die optimale Wirkung der Präparate bestimmt, die infolge unterschiedlicher Resorption zu verschiedenen Zeitpunkten nach der Behandlung liegt.All compounds have been tested on the rat after oral administration been. In each case, the time for the optimal effect of the preparations was determined, as a result of different absorption at different points in time after treatment lies.

Außer der Dosis letalis (LDSO) wurde noch diejenige Dosierung ermittelt, welche bei 50 % der Tiere neurologische und sonstige Toxizitätserscheinungen verursacht. Diese Dosierung wurde als TD" in der Tabelle angegeben.In addition to the lethal dose (LDSO), the dose was also determined which causes neurological and other toxicity symptoms in 50% of the animals. This dosage was given as TD "in the table.

Als neurologische Toxizitätssymptome wurden gewertet: Störung der Körperstellreflexe, die Ataxie, Zickzackgang, Zittern, Somnolenz oder Störung des Muskeltonus. Traten andere Nebenerscheinungen, wie z. B. Hämoptoe oder Hyperpnoe, schon in niederen Dosierungen auf, so wurden diese als Endwert der Toxizitätsbestimmung gewertet. Elektroschock Cardiazolschock Verbindung LDoo TD" ED Index Index @o TD" EDSO TD" g/ kg g/kg g/kg EDso g/kg EDSo 5-Phenyl-5-tert.-butyl-hydantoin .................... 10,0 1,50 0,057 26,0 0,074 20,3 5-Phenyl-5-isobutyl-hydantoin ...................... 1,25 0,45 0,075 6,0 0,080 5,6 5-Phenyl-5-n-butyl-hydantoin . . . . . . . . . . . . . . . . . . . . . . . 5,5 > 6,0 0,62 > 9,7 0,46 > 13,0 5-Phenyl-5-(1-methyl-propyl)-hydantoin . . . . . . . . . . . . . . > 10,0 > 10,0 1,50 > 6,6 0,46 > 21,0 5-Phenyl-5-isopropyl-hydantoin ..................... 1,4 0,160 0,056 2,85 0,042 3,80 5-Phenyl-5-n-propyl-hydantoin ...................... 1,6 0,18 0,066 2,7 0,060 3,0 5,5-Diphenyl-hydantoin ............................ 1,6 0,125 0,018 6,9 keine Wirkung 5-Methyl-5-tert.-butyl-hydantoin .................... 2,3 0,57 1,10 0,52 0,27 2,1 Aus vorstehender Tabelle ist ersichtlich, daß das 5-Phenyl-5-tert.-butyl-hydantoin die günstigsten Indizes zeigt. Diese übertreffen diejenigen von 5, 5-Diphenylhydantoin und der anderen chemisch nahestehenden Verbindungen zumeist um ein Mehrfaches. Das 5-Phenyl-5-tert.-butyl-hydantoin wird durch Umsetzen von Pivalophenon (Phenyl-tert.-butyl-keton) mit Alkalicyanid und Ammoniumcarbonat, gegebenenfalls unter Kohlensäureüberdruck, in der Wärme gewonnen. Bei dieser grundsätzlich glatt verlaufenden Reaktion ist die Ausbeute gut. Sie kann noch durch Variieren der Gewichtsanteile der Ausgangsstoffe, des Druckes, der Reaktionszeit und der Temperatur gesteuert werden.The following neurological symptoms of toxicity were rated: disturbance of the body reflexes, ataxia, zigzag gait, tremors, somnolence or disturbance of the muscle tone. Did other side effects such as B. haemoptosis or hyperpnea, even in low doses, these were taken as the final value of the toxicity determination. Electric shock cardiazole shock Link LDoo TD "ED Index Index @o TD " EDSO TD" g / kg g / kg g / kg EDso g / k g EDSo 5-phenyl-5-tert-butyl-hydantoin .................... 10.0 1.50 0.057 26.0 0.074 20.3 5-phenyl-5-isobutyl-hydantoin ...................... 1.25 0.45 0.075 6.0 0.080 5.6 5-phenyl-5-n-butyl hydantoin. . . . . . . . . . . . . . . . . . . . . . . 5.5> 6.0 0.62> 9.7 0.46> 13.0 5-phenyl-5- (1-methyl-propyl) hydantoin. . . . . . . . . . . . . . >10.0> 10.0 1.50> 6.6 0.46> 21.0 5-phenyl-5-isopropyl-hydantoin ..................... 1.4 0.160 0.056 2.85 0.042 3.80 5-phenyl-5-n-propyl-hydantoin ...................... 1.6 0.18 0.066 2.7 0.060 3.0 5,5-diphenyl-hydantoin ............................ 1.6 0.125 0.018 6.9 no effect 5-methyl-5-tert-butyl-hydantoin .................... 2.3 0.57 1.10 0.52 0.27 2.1 It can be seen from the table above that 5-phenyl-5-tert.-butylhydantoin shows the most favorable indices. These exceed those of 5, 5-diphenylhydantoin and the other chemically related compounds mostly several times over. The 5-phenyl-5-tert-butyl-hydantoin is obtained by reacting pivalophenone (phenyl-tert-butyl-ketone) with alkali metal cyanide and ammonium carbonate, if necessary under excess carbonic acid pressure, in the heat. In this basically smooth reaction, the yield is good. It can also be controlled by varying the proportions by weight of the starting materials, the pressure, the reaction time and the temperature.

Beispiel 486,6 g (3 Mol) Pivalophenon werden mit 234 g (3,6 Mol) Kaliumcyanid und 480 g handelsüblichem Ammoniumcarbonat in 3,61 50°/oigem Äthylalkohol in einem Autoklav unter 40 atü C 02 Druck 20 Stunden auf 100°C erhitzt. Die erhaltene Fällung wird abgesaugt und mit Wasser und Äther gewaschen. Nach dem Trocknen erhält man 657 g (94°/o der Theorie) 5-Phenyl-5-tert.-butyl-hydantoin, das nach dem Umkristallisieren aus Methanol bei 271 bis 273°C schmilzt.Example 486.6 g (3 mol) of pivalophenone are mixed with 234 g (3.6 mol) of potassium cyanide and 480 g of commercial ammonium carbonate in 3.61 50% ethyl alcohol in one Autoclave heated to 100 ° C for 20 hours under 40 atmospheric pressure. The precipitate obtained is suctioned off and washed with water and ether. After drying, one obtains 657 g (94% of theory) of 5-phenyl-5-tert-butyl-hydantoin, which after recrystallization melts from methanol at 271 to 273 ° C.

Claims (1)

PATENTANSPRUCH: Verfahren zur Herstellung einer neuen Hydantoinverbindung, dadurch gekennzeichnet, daß man Pivalophenon mit Allkalicyanid und Ammoniumcarbonat, gegebenenfalls unter Kohlensäureüberschuß, in der Wärme umsetzt und das dabei entstehende 5-Phenyl-5-tert.-butyl-hydantoin nach an sich üblichen Methoden isoliert. In Betracht gezogene Druckschriften: Deutsche Patentschrift Nr. 817152.PATENT CLAIM: Process for the production of a new hydantoin compound, characterized in that pivalophenone with alkali metal cyanide and ammonium carbonate, possibly with excess carbonic acid, converts in the heat and the resulting 5-Phenyl-5-tert.-butylhydantoin isolated by conventional methods. Into consideration Printed publications: German Patent No. 817152.
DER20915A 1957-04-05 1957-04-05 Process for the preparation of a new hydantoin compound Pending DE1041502B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
DER20915A DE1041502B (en) 1957-04-05 1957-04-05 Process for the preparation of a new hydantoin compound

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DER20915A DE1041502B (en) 1957-04-05 1957-04-05 Process for the preparation of a new hydantoin compound

Publications (1)

Publication Number Publication Date
DE1041502B true DE1041502B (en) 1958-10-23

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Family Applications (1)

Application Number Title Priority Date Filing Date
DER20915A Pending DE1041502B (en) 1957-04-05 1957-04-05 Process for the preparation of a new hydantoin compound

Country Status (1)

Country Link
DE (1) DE1041502B (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1212974B (en) * 1962-09-12 1966-03-24 Dainippon Pharmaceutical Co Process for the preparation of 5,5-diphenyl-N-carboaethoxyhydantoin

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1212974B (en) * 1962-09-12 1966-03-24 Dainippon Pharmaceutical Co Process for the preparation of 5,5-diphenyl-N-carboaethoxyhydantoin

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