DE290531C - - Google Patents
Info
- Publication number
- DE290531C DE290531C DENDAT290531D DE290531DA DE290531C DE 290531 C DE290531 C DE 290531C DE NDAT290531 D DENDAT290531 D DE NDAT290531D DE 290531D A DE290531D A DE 290531DA DE 290531 C DE290531 C DE 290531C
- Authority
- DE
- Germany
- Prior art keywords
- alcohol
- hours
- parts
- diketopyrrolidines
- ammonia
- 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.)
- Active
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- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 2
- 150000002366 halogen compounds Chemical class 0.000 claims description 2
- 238000000034 method Methods 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 10
- 150000001875 compounds Chemical group 0.000 description 8
- 239000007858 starting material Substances 0.000 description 7
- 230000001476 alcoholic Effects 0.000 description 6
- 238000007112 amidation reaction Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 238000002844 melting Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- NMCUIPGRVMDVDB-UHFFFAOYSA-L Iron(II) chloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- -1 pyrrolidine compound Chemical class 0.000 description 3
- HUMNYLRZRPPJDN-UHFFFAOYSA-N Benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- FXLOVSHXALFLKQ-UHFFFAOYSA-N 4-Methylbenzaldehyde Chemical compound CC1=CC=C(C=O)C=C1 FXLOVSHXALFLKQ-UHFFFAOYSA-N 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K Iron(III) chloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- VMPITZXILSNTON-UHFFFAOYSA-N O-Anisidine Chemical compound COC1=CC=CC=C1N VMPITZXILSNTON-UHFFFAOYSA-N 0.000 description 1
- 206010039073 Rheumatoid arthritis Diseases 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 229940095076 benzaldehyde Drugs 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 201000005569 gout Diseases 0.000 description 1
- BAVYZALUXZFZLV-UHFFFAOYSA-N methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000001376 precipitating Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D207/36—Oxygen or sulfur atoms
- C07D207/38—2-Pyrrolones
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
Description
KAISERLICHESIMPERIAL
PATENTAMT.PATENT OFFICE.
PATENTSCHRIFTPATENT LETTERING
-M 290531 ■'-KLASSE 12p. GRUPPE -M 290531 ■ 'CLASS 12p. GROUP
in BERLIN.in Berlin.
Verfahren zur Darstellung von Diketopyrrolidinderivaten. Patentiert im Deutschen Reiche vom 23. August 1914 ab.Process for the preparation of diketopyrrolidine derivatives. Patented in the German Empire on August 23, 1914.
Unterwirft man Diketopyrrolidine der allgemeinen FormelSubjecting diketopyrrolidines to the general formula
OC OCOC OC
τι C H —τι C H -
CH-R1 CH-R 1
N — RNO
ίο (worin R und R1 beliebige Radikale und R2 ein Säureradikal bedeuten) bzw. Halogenverbindungen solcher Diketopyrrolidine bei erhöhter Temperatur der Einwirkung von Ammoniak, so erhält man Diketopyrrolidinderivatej die zu therapeutischen Zwecken, insbesondere als Heilmittel gegen Gicht und Gelenkrheumatismus, Verwendung finden sollen. Die Reaktion verläuft in der Weise, daß unter Austritt von Wasser eine Aminogruppe in die Pyrrolidinverbindung eintritt, wahrscheinlich in die 4-Stellung.ίο (where R and R 1 are any radicals and R 2 is an acid radical) or halogen compounds of such diketopyrrolidines at elevated temperatures under the action of ammonia, diketopyrrolidine derivatives are obtained which are intended to be used for therapeutic purposes, in particular as a remedy for gout and rheumatoid arthritis. The reaction proceeds in such a way that, with the escape of water, an amino group enters the pyrrolidine compound, probably in the 4-position.
i. Amidierung des 1 ■ 2-Diphenyl-3~acetyl-4 · 5-diketopyrrolidins.i. Amidation of 1 ■ 2-diphenyl-3 ~ acetyl-4 · 5-diketopyrrolidines.
30 Teile des Ausgangsstoffes (vgl. Berichte 3130 parts of the starting material (see reports 31
[1898], S. 1307) werden in 200 Teilen ioprozentigem, alkoholischem Ammoniak 4 Stunden auf 170 bis i8o° erhitzt. Die sich allmählich ausscheidenden Kristalle werden aus verdünntem Alkohol umkristallisiert und schmelzen dann gegen 220 °. Die geschmacklosen gelblichen Kristalle, die in Alkohol löslich, in Äther unlöslich sind, geben nicht mehr die charakteristische Eisenchloridfärbung des Ausgangsstoffes. Durch heißes Alkali wird kein Ammoniak abgespalten. Die empirische Zusammensetzung der Verbindung entspricht der Formel C18H16O2N2.[1898], p. 1307) are heated in 200 parts of 10% alcoholic ammonia to 170 to 180 ° for 4 hours. The gradually separating crystals are recrystallized from dilute alcohol and then melt towards 220 °. The tasteless yellowish crystals, which are soluble in alcohol and insoluble in ether, no longer give the characteristic iron chloride color of the starting material. No ammonia is split off by hot alkali. The empirical composition of the compound corresponds to the formula C 18 H 16 O 2 N 2 .
2. Amidierung des bromierten ΐ·2-Diphenyl-3-acetyl-4 · 5-diketopyrrolidins. 2. Amidation of the brominated ΐ · 2-diphenyl-3-acetyl-4 · 5-diketopyrrolidines.
10 Teile des Ausgangsstoffes (durch Einwirkung der berechneten Menge Brom auf eine Suspension des 1 · 2 - Diphenyl-3-acetyl-4 · 5-diketopyrrolidins in heißem Chloroform erhalten; das bromierte Produkt scheidet sich beim Erkalten aus und bildet weiße Nadeln vom Schmelzpunkt 189 °, löslich in organischen Lösungsmitteln mit Ausnahme von Petroläther, mit Eisenchloridlösung eine braunrote Färbung gebend) werden in 50 Teile wässeriges Ammoniak (vom spez. Gew. 0,96) eingetragen. Die sich ausscheidende Kristallmasse besteht aus rosettenförmig geordneten, flachen, hellrosa gefärbten Nadeln, die sich bei 254 bis 256 ° zersetzen. Die Verbindung (C18 H15 Br O2 N2) spaltet beim Erhitzen mit Alkalien Ammoniak ab und ist in den gebräuchlichsten organischen Lösungsmitteln sehr schwer löslich.10 parts of the starting material (obtained by the action of the calculated amount of bromine on a suspension of 1 · 2-diphenyl-3-acetyl-4 · 5-diketopyrrolidine in hot chloroform; the brominated product separates out on cooling and forms white needles with a melting point of 189 °, soluble in organic solvents with the exception of petroleum ether, giving a brown-red color with ferric chloride solution) are added to 50 parts of aqueous ammonia (with a specific weight of 0.96). The precipitating crystal mass consists of rosette-shaped, flat, light pink colored needles that decompose at 254 to 256 °. The compound (C 18 H 15 Br O 2 N 2 ) splits off ammonia when heated with alkalis and is very sparingly soluble in the most common organic solvents.
3· Amidierung des i-o-Methoxyphenyl-2-p-tolyl-3-acetyl-4·5-diketoρyrro- 3 · amidation of i-o-methoxyphenyl-2-p-tolyl-3-acetyl-4 · 5-diketoρyrro-
lidins.lidins.
30 Teile des Ausgangsstoffes (erhalten durch Einwirkung molekularer Mengen o-Anisidin, p-Toluylaldehyd und Acetylbrenztraubensäureester in Benzol während 24 Stunden oder 1J2 stündiges Kochen; Schmelzpunkt 217° aus Alkohol oder Benzol kristallisiert, löslich in Alkohol und Alkalien, die Eisenchloridreaktion gebend) werden in 200 Teilen ioprozentigem, alkoholischem Ammoniak 5 Stunden auf 170 bis i8o° erhitzt. Nach 12 Stunden wird die Lösung in viel schwefelsäurehaltiges Wasser gegossen, der Niederschlag nach längerem Stehen gereinigt und aus 3oprozentigem Alkohol umkristallisiert. Die Verbindung, deren empirische Zusammensetzung der Formel C20 H20 O3 N2 entspricht, bildet geschmacklose Kristalle vom Schmelzpunkt 143 bis 145° und zeigt im allgemeinen die gleichen Eigenschaften wie die im Beispiel 1 beschriebene Verbindung.30 parts of the starting material (obtained through the action of molecular amounts of o-anisidine, p-toluylaldehyde and acetylpyruvic acid ester in benzene for 24 hours or 1 and 2 hours of boiling; melting point 217 ° crystallized from alcohol or benzene, soluble in alcohol and alkalis, giving the iron chloride reaction) are heated in 200 parts of 10% alcoholic ammonia for 5 hours to 170 to 180 °. After 12 hours, the solution is poured into plenty of water containing sulfuric acid, the precipitate is purified after standing for a long time and recrystallized from 3% alcohol. The compound, the empirical composition of which corresponds to the formula C 20 H 20 O 3 N 2 , forms tasteless crystals with a melting point of 143 to 145 ° and generally shows the same properties as the compound described in Example 1.
4. Amidierung des i-Methyl-2-phenyl-3-acetyl-4 · 5-diketopyrrolidins. '4. Amidation of i-methyl-2-phenyl-3-acetyl-4 · 5-diketopyrrolidines. '
30 Teile des Ausgangsstoffes (dieser wird in folgender Weise erhalten. Man löst molekulare Mengen Methylamin und Benzaldehyd in absolutem Alkohol, gibt dazu unter Umschütteln eine absolut alkoholische Lösung von Acetylbrenztraubensäuseester und läßt 24 Stunden stehen. Die Verbindung bildet Kristalle vom Schmelzpunkt 215 bis 216 ° aus Essigester, ist löslich in Alkohol, unlöslich in Wasser, Äther und Petroläther und gibt die Eisenchloridreaktion) werden mit der gleichen Menge alkoholischem Ammoniak wie im Beispiel 3 5 Stunden auf 170 bis 180 ° erhitzt und die gelblich gefärbten Kristalle nach 24 Stunden aus verdünntem Alkohol umkristallisiert. Die empirische Zusammensetzung der Verbindung, die bei 260° unter Zersetzung schmilzt, entspricht der Formel C13 H13 O3 N2, das Produkt ist löslich in Alkohol, heißem Wasser, unlöslich in Benzol und Äther.30 parts of the starting material (this is obtained in the following manner. Molecular amounts of methylamine and benzaldehyde are dissolved in absolute alcohol, an absolutely alcoholic solution of acetylpyruvic acid ester is added with shaking and left to stand for 24 hours. The compound forms crystals with a melting point of 215-216 ° Ethyl acetate, is soluble in alcohol, insoluble in water, ether and petroleum ether and gives the iron chloride reaction) are heated to 170 to 180 ° for 5 hours with the same amount of alcoholic ammonia as in Example 3 and the yellowish colored crystals are recrystallized from dilute alcohol after 24 hours . The empirical composition of the compound, which melts at 260 ° with decomposition, corresponds to the formula C 13 H 13 O 3 N 2 , the product is soluble in alcohol, hot water, insoluble in benzene and ether.
5- Amidierung des ι · 2-Diphenyl-4'5-diketopyrrolidin-3"C ar bonsäureäthylesters. 5- amidation of ι · 2-diphenyl-4'5-diketopyrrolidine-3 "C ar bonsäureäthylester.
21 Teile des Ausgangsstoffes (vgl. Chem. Centralbl. 1907, II, S. 1787) werden mit 150 ecm ioprozentigem, alkoholischem Ammoniak, wie im Beispiel 2 und 3 angegeben, erhitzt. Die nach 24 Stunden abgesaugten Kristalle werden aus verdünntem Alkohol umkristallisiert. Die färb- und geschmacklose Verbindung (C19H18O3N2) schmilzt bei 160 bis 162 ° und ist löslich in Alkohol, Äther, Benzol, unlöslieh in Wasser, Petroläther, Alkali.21 parts of the starting material (cf. Chem. Centralbl. 1907, II, p. 1787) are heated with 150 ecm 10% alcoholic ammonia, as indicated in Examples 2 and 3. The crystals sucked off after 24 hours are recrystallized from dilute alcohol. The colorless and tasteless compound (C 19 H 18 O 3 N 2 ) melts at 160 to 162 ° and is soluble in alcohol, ether, benzene, insoluble in water, petroleum ether, alkali.
6. Amidierung des 1 · 2-3-Triphenyl-4 •5-diketopyrrolidins.6. Amidation of the 1 · 2-3-triphenyl-4 • 5-diketopyrrolidines.
18 Teile des Ausgangsstoffes (vgl. Berichte 42 [1909], S. 4076) werden auf 170 bis 180° 5 Stunden im Rohr mit 150 Teilen ioprozentigem, alkoholischem Ammoniak erhitzt. Die nach 24 Stunden abgesaugten Kristalle werden gereinigt und aus 96 prozentigern Alkohol umkristallisiert. Die färb- und geschmacklosen Kristalle schmelzen bei 169 bis 171 ° und sind in Wasser und Petroläther unlöslich, in Äther, Benzol, Alkohol löslich. Die empirische Zusammensetzung der Verbindung entspricht der Formel C22 H18 O N2.18 parts of the starting material (cf. Reports 42 [1909], p. 4076) are heated to 170 ° to 180 ° for 5 hours in a tube with 150 parts of 10% alcoholic ammonia. The crystals sucked off after 24 hours are cleaned and recrystallized from 96 percent alcohol. The colorless and tasteless crystals melt at 169 to 171 ° and are insoluble in water and petroleum ether, soluble in ether, benzene and alcohol. The empirical composition of the compound corresponds to the formula C 22 H 18 ON 2 .
Claims (1)
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE290531C true DE290531C (en) |
Family
ID=545489
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DENDAT290531D Active DE290531C (en) |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE290531C (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2490462A (en) * | 1942-11-04 | 1949-12-06 | Borden Co | Halogenation products of aldehydes of mono-heteroatomic five membered rings and methods of making same |
-
0
- DE DENDAT290531D patent/DE290531C/de active Active
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2490462A (en) * | 1942-11-04 | 1949-12-06 | Borden Co | Halogenation products of aldehydes of mono-heteroatomic five membered rings and methods of making same |
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