DE1009187B - Process for the preparation of 3-amino-oxazolidonen- (2) - Google Patents
Process for the preparation of 3-amino-oxazolidonen- (2)Info
- Publication number
- DE1009187B DE1009187B DEE6832A DEE0006832A DE1009187B DE 1009187 B DE1009187 B DE 1009187B DE E6832 A DEE6832 A DE E6832A DE E0006832 A DEE0006832 A DE E0006832A DE 1009187 B DE1009187 B DE 1009187B
- Authority
- DE
- Germany
- Prior art keywords
- amino
- diethyl carbonate
- preparation
- reaction
- heated
- 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
- 238000000034 method Methods 0.000 title claims description 5
- 238000002360 preparation method Methods 0.000 title claims description 3
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 238000009833 condensation Methods 0.000 claims description 3
- 230000005494 condensation Effects 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 239000000203 mixture Substances 0.000 description 8
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 3
- NIHYUMUIKWTKQE-UHFFFAOYSA-N 3-amino-1,3-oxazolidin-2-id-4-one Chemical class NN1[CH-]OCC1=O NIHYUMUIKWTKQE-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- WDGWKYLQWAUVFT-UHFFFAOYSA-N 2-hydrazinylhexan-1-ol Chemical compound CCCCC(CO)NN WDGWKYLQWAUVFT-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- PQXKWPLDPFFDJP-UHFFFAOYSA-N 2,3-dimethyloxirane Chemical compound CC1OC1C PQXKWPLDPFFDJP-UHFFFAOYSA-N 0.000 description 1
- BTANRVKWQNVYAZ-UHFFFAOYSA-N 2-butanol Substances CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 1
- VZIQXGLTRZLBEX-UHFFFAOYSA-N 2-chloro-1-propanol Chemical compound CC(Cl)CO VZIQXGLTRZLBEX-UHFFFAOYSA-N 0.000 description 1
- XHXRVPVNPLMWGI-UHFFFAOYSA-N 2-hydrazinylhexanoic acid Chemical compound CCCCC(NN)C(O)=O XHXRVPVNPLMWGI-UHFFFAOYSA-N 0.000 description 1
- CPCFSCALAJVNSL-UHFFFAOYSA-N 2h-1,3-oxazol-3-amine Chemical compound NN1COC=C1 CPCFSCALAJVNSL-UHFFFAOYSA-N 0.000 description 1
- SSZWWUDQMAHNAQ-UHFFFAOYSA-N 3-chloropropane-1,2-diol Chemical compound OCC(O)CCl SSZWWUDQMAHNAQ-UHFFFAOYSA-N 0.000 description 1
- RUPFLBXVOITJRE-UHFFFAOYSA-N 3-hydrazinylbutan-2-ol Chemical compound CC(O)C(C)NN RUPFLBXVOITJRE-UHFFFAOYSA-N 0.000 description 1
- 125000005910 alkyl carbonate group Chemical group 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- -1 lithium aluminum hydride Chemical compound 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 150000005063 oxadiazines Chemical class 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Description
Verfahren zur Herstellung -von 3-Amino-oxazolidonen-(2) 3-Amino-oxazolidone (2) der allgemeinen Formel in welcher R, R1, R2 und R3 Wasserstoff, niedere Alky1- oder Oxyalkylreste bedeuten und gleich oder verschieden sein können, sind bisher noch nicht beschriworden. Sie sind besonders als Zwischenprodukte zur Herstellung hochwertiger Chemotherapeutika wertvoll.Process for the preparation of 3-amino-oxazolidones- (2) 3-amino-oxazolidones (2) of the general formula in which R, R1, R2 and R3 denote hydrogen, lower alkyl or oxyalkyl radicals and can be identical or different, have not yet been described. They are particularly valuable as intermediate products in the manufacture of high-quality chemotherapeutic agents.
Es wurde nun gefunden, daß 3 Amino-oxa,zolidine-(2) der angegebenen Formel mit guter Ausbeute erhalten werden können, wenn man ß-Oxyalkylhydrazine entsprechender Zusammensetzung und Alkylcarbonate, vorzugsweise Diäthylcarbonat, im Sinne des nachstehenden Reaktionsschemas in Gegenwart alkalischer Kondensationsmittel erhitzt: Zweckmäßig wird der während der Reaktion gebildete Alkohol durch Destillation laufend entfernt. Der Verlauf der Reaktion wird durch die Anwesenheit von Alkalimetallkatalysatoren, z. B. Natriummethylat, begünstigt.It has now been found that 3 amino-oxa, zolidine- (2) of the formula given can be obtained in good yield if ß-oxyalkylhydrazines of the corresponding composition and alkyl carbonates, preferably diethyl carbonate, are heated in the presence of alkaline condensing agents in accordance with the following reaction scheme: The alcohol formed during the reaction is expediently continuously removed by distillation. The course of the reaction is controlled by the presence of alkali metal catalysts, e.g. B. sodium methylate, favored.
Der erfindungsgemäße Reaktionsverlauf ist überraschend und neu; denn man hätte auf Grund der Vorliteratur (J. von A 1 p h e n , Rec. Trav. chim. Pay-Bas, 47, S. 909 bis 919 [1928]) eher annehmen können, daß die Reaktion an der primären Aminogruppe angreift und Oxadiazine gebildet werden.The course of the reaction according to the invention is surprising and new; because on the basis of the previous literature (J. von A 1 p h e n, Rec. Trav. chim. Pay-Bas, 47, pp. 909 to 919 [1928]) can rather assume that the reaction at the primary Amino group attacks and oxadiazines are formed.
Das Verfahren der Erfindung wird durch die nachfolgenden Beispiele erläutert, ohne daß damit eine Beschränkung auf die dort mitgeteilten Daten ausgesprochen werden soll. Für die Herstellung der Ausgangsstoffe wird im Rahmen der vorliegenden Erfindung kein Schutz begehrt. Beispiel 1 3-Amino-oxazol i don- (2) Eine Mischung aus 15,4g ß-Oxyäthylhydrazin, 30 ccm Diäthylcarbonat und einer Lösung von Ob g Natrium in 10 ccm Methanol wird in einen mit einer V-igreuxsäuile@ ausgestatteten Kolben gegeben. Die Mischung wird erhitzt und das in der Reaktion entstandene Äthanot langsam abdestilliert. Wenn die Destillation des Äthanols nach etwa 1 Stunde aufhört, wird der Rückstand gekühlt und, mit 10 ccm Äthanol verdünnt. Der erhaltene Niederschlag wird abfiltriert und getrocknet. Man erhält (in 69°/aiger Ausbeute) 14,2 g 3-Amino-oxazolidon-(2) vom F. 55 his 62°. Beim Umkristallisieren aus Äthanol steigt der Schmelzpunkt auf 69 bis 71°.The method of the invention is illustrated by the following examples, without any restriction to the data reported there. No protection is sought for the production of the starting materials in the context of the present invention. Example 1 3-Amino-oxazole i don- (2) A mixture of 15.4 g of β-oxyethylhydrazine, 30 cc of diethyl carbonate and a solution of Ob g of sodium in 10 cc of methanol is placed in a flask equipped with a V-igreux column®. The mixture is heated and the ethanol produced in the reaction is slowly distilled off. When the distillation of the ethanol ceases after about 1 hour, the residue is cooled and diluted with 10 cc of ethanol. The precipitate obtained is filtered off and dried. 14.2 g of 3-amino-oxazolidone- (2) with a melting point of 55 to 62 ° are obtained (in a yield of 69%). When recrystallizing from ethanol, the melting point rises to 69 to 71 °.
Beispiel 2 3-Am-ino-5-methyl-oxazodidon-(2) Eine Mischung von 45 g 2-Oxypropylhy.drazin (das durch. Kondensation von Propylenchlorhydrin mit Hydrazinhydrat hergestellt wurde), 74 ccm Diäthylcarbonat und einer Lösung von 1,4 g Natrium in 16 ccm Methanol wird in einen mit einer Vigreuxsäule versehenen Kolben gegeben. Die Mischung wird erhitzt und das in der Reaktion gebildete Äthanol langsam abdestilliert. Wenn die Destillation des Äthanols nach etwa 1 Stunde aufhört, wird der Rückstand gekühlt und mit etwa 20 ccm Isopropanol verdünnt. Der erhaltene Niederschlag wird durch Filtration abgetrennt. Die Umkristallisation. aus Isopropanol ergibt (in 24,8o/oiger Ausbeute) 14,4 g 3-Amino-5-methyl-oxazolidon-(2) vom F. 40 bis 42°. Die reine Verbindung schmilzt nach mehrmaligem Umkristalli-sieren bei 50,3 bis 50,5°.Example 2 3-Am-ino-5-methyl-oxazodidone- (2) A mixture of 45 g of 2-oxypropylhydrazine (prepared by condensation of propylene chlorohydrin with hydrazine hydrate), 74 cc of diethyl carbonate and a solution of 1.4 g of sodium in 16 cc of methanol is placed in a flask equipped with a Vigreux column. The mixture is heated and the ethanol formed in the reaction is slowly distilled off. When the distillation of the ethanol ceases after about 1 hour, the residue is cooled and diluted with about 20 cc of isopropanol. The precipitate obtained is separated off by filtration. The recrystallization. from isopropanol gives (in 24.8% yield) 14.4 g of 3-amino-5-methyl-oxazolidone- (2) with a melting point of 40 ° to 42 °. The pure compound melts after repeated recrystallization at 50.3 to 50.5 °.
Beispiel 3 3-Amino-4, 5-dimethyl-oxazolidon-(2) Zu einer Lösung von 1,3 g Natrium in 15 ccm Methanol werden 18,7 g 3-Hydrazino-2-butanol (durch Kondensation von 2, 3 -Epoxybutan mit Hydrazinhydrat hergestellt) und 23,5 g Diäthylcarbonat gegeben. Die Mischung wird unter Rühren 1 Stunde am Rückfluß erhitzt; dann werden Methanol, Äthanol, überschüssiges Diäthylcarbonat und nicht umgesetztes 3-Hydrazin-2-butanol durch Vakuumdestillation entfernt. Ausbeute 45°/o der Theorie.Example 3 3-Amino-4,5-dimethyl-oxazolidone- (2) 18.7 g of 3-hydrazino-2-butanol (prepared by condensation of 2,3-epoxybutane with hydrazine hydrate) and 23.5 g of diethyl carbonate are added to a solution of 1.3 g of sodium in 15 cc of methanol. The mixture is refluxed with stirring for 1 hour; then methanol, ethanol, excess diethyl carbonate and unreacted 3-hydrazine-2-butanol are removed by vacuum distillation. Yield 45% of theory.
Beispiel 4 3-Amino,-4-n-butyl-oxazoli-don-(2) Eine Mischung aus 9,5 g 2-Hydrazino-1-hexanol (das durch Reduktion von a-Hydrazinocapronsäureäthyloster mit Lithiumaluminiumhydrid hergestellt wurde), 10g Diäthylcarbonat und einer Lösung von 0,35 g Natrium in 5 ccm Methanol wird 2 Stunden am Rückfluß erhitzt. Eine kleine Menge unlöslichen Materials wird durch Filtration entfernt und das Filtrat im Vakuum destilliert. Zuerst wird ein Vorlauf aus Methanol, Äthanol, überschüssigeren Diäthylcarbonat und nicht umgesetztes 2-Hydrazino, 1-hexanol urhalben. Das Reaktionsprodukt, 2-Amino-4-butyl-oxazalidon-(2), destilliert bei 135°/0,7 mm. Ausbeute 46°/o der Theorie.Example 4 3-Amino, -4-n-butyl-oxazolidone- (2) A mixture of 9.5 g of 2-hydrazino-1-hexanol (which was prepared by reducing α-hydrazinocaproic acid ethyloster with lithium aluminum hydride), 10 g of diethyl carbonate and a solution of 0.35 g of sodium in 5 cc of methanol is refluxed for 2 hours. A small amount of insoluble material is removed by filtration and the filtrate is distilled in vacuo. First, a first run of methanol, ethanol, excess diethyl carbonate and unreacted 2-hydrazino, 1-hexanol is used. The reaction product, 2-amino-4-butyl-oxazalidone- (2), distilled at 135 ° / 0.7 mm. Yield 46% of theory.
Beispiel 5 3-Am.ino-5-oxymethyl-oxazolidon-(2) Eine Lösung aus 43 g Natriumhydroxyd in 250 g 100°/oigem Hydrazinhydrat wird auf 40° erwärmt und dann tropfenweise im Zeitraum von 15 Minuten bei auf 110° ansteigender Temperatur mit: 110 g Glycerina-monochlorhydrin behandelt. Das Reaktionsgemisch wird dann 80 Minuten auf dem Dampfbad erhitzt; Wasser und überschüssiges Hydrazin werden im Vakuum entfernt. Der Rest wird mit absolutem Alkohol verdünnt und das Natriumchlorid abfiltriert. Zur Entfernung des Alkohols wird das Filtrat im Vakuum -konzentriert. Zu dem zurückbleibenden Öl werden 150 ccm Diäthylcarbonat und eine Lösung von 1 g Natrium in 55 ccm Methanol gegeben. Die Mischung wird erhitzt und das in der Reaktion gebildete Äthanol in 31/2 Stunden langsam abdestilliert. Ausbeute 34°/o der Theorie.Example 5 3-Am.ino-5-oxymethyl-oxazolidone- (2) A solution of 43 g of sodium hydroxide in 250 g of 100% hydrazine hydrate is heated to 40 ° and then treated dropwise over a period of 15 minutes at a temperature rising to 110 ° with: 110 g of glycerine monochlorohydrin. The reaction mixture is then heated on the steam bath for 80 minutes; The water and excess hydrazine are removed in vacuo. The remainder is diluted with absolute alcohol and the sodium chloride is filtered off. The filtrate is concentrated in vacuo to remove the alcohol. 150 cc of diethyl carbonate and a solution of 1 g of sodium in 55 cc of methanol are added to the remaining oil. The mixture is heated and the ethanol formed in the reaction is slowly distilled off in 3 1/2 hours. Yield 34% of theory.
Claims (2)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US1009187XA | 1952-02-28 | 1952-02-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1009187B true DE1009187B (en) | 1957-05-29 |
Family
ID=22282201
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEE6832A Pending DE1009187B (en) | 1952-02-28 | 1953-02-27 | Process for the preparation of 3-amino-oxazolidonen- (2) |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1009187B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2437390A (en) * | 1948-03-09 | Z-oxazolidone compounds and proc |
-
1953
- 1953-02-27 DE DEE6832A patent/DE1009187B/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2437390A (en) * | 1948-03-09 | Z-oxazolidone compounds and proc |
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