DE96492C - - Google Patents
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- Publication number
- DE96492C DE96492C DENDAT96492D DE96492DA DE96492C DE 96492 C DE96492 C DE 96492C DE NDAT96492 D DENDAT96492 D DE NDAT96492D DE 96492D A DE96492D A DE 96492DA DE 96492 C DE96492 C DE 96492C
- Authority
- DE
- Germany
- Prior art keywords
- acid
- esters
- cone
- ammonia
- amide
- 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.)
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- 150000002148 esters Chemical class 0.000 claims description 11
- AVDLFIONKHGQAP-UHFFFAOYSA-N 4-Nitrophenoxyacetic acid Chemical compound OC(=O)COC1=CC=C([N+]([O-])=O)C=C1 AVDLFIONKHGQAP-UHFFFAOYSA-N 0.000 claims description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 7
- CPABIIMOBRMZNS-UHFFFAOYSA-N 2-(4-acetamidophenoxy)acetamide Chemical compound CC(=O)NC1=CC=C(OCC(N)=O)C=C1 CPABIIMOBRMZNS-UHFFFAOYSA-N 0.000 claims description 4
- 150000001408 amides Chemical class 0.000 claims description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 4
- 238000006640 acetylation reaction Methods 0.000 claims description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 2
- 238000000034 method Methods 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 238000009835 boiling Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 5
- LYJCGBYEVXKOST-UHFFFAOYSA-N 2-(4-acetamidophenoxy)acetic acid Chemical compound CC(=O)NC1=CC=C(OCC(O)=O)C=C1 LYJCGBYEVXKOST-UHFFFAOYSA-N 0.000 description 4
- 229960000583 Acetic Acid Drugs 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000000155 melt Substances 0.000 description 3
- 231100000486 side effect Toxicity 0.000 description 3
- KRVSOGSZCMJSLX-UHFFFAOYSA-L Chromic acid Chemical compound O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 2
- 230000001476 alcoholic Effects 0.000 description 2
- 125000003368 amide group Chemical group 0.000 description 2
- 230000001754 anti-pyretic Effects 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 230000000875 corresponding Effects 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- IYJAUHBAFQALLE-UHFFFAOYSA-N 2-(4-nitrophenoxy)acetamide Chemical compound NC(=O)COC1=CC=C([N+]([O-])=O)C=C1 IYJAUHBAFQALLE-UHFFFAOYSA-N 0.000 description 1
- 101700066512 COGC Proteins 0.000 description 1
- HFFLGKNGCAIQMO-UHFFFAOYSA-N Chloral Chemical compound ClC(Cl)(Cl)C=O HFFLGKNGCAIQMO-UHFFFAOYSA-N 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000000095 emetic Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000011068 load Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000003000 nontoxic Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N oxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propanol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N tin hydride Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- CVNKFOIOZXAFBO-UHFFFAOYSA-J tin(4+);tetrahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[Sn+4] CVNKFOIOZXAFBO-UHFFFAOYSA-J 0.000 description 1
- IVNZBWNBYXERPK-DZGBHZPSSA-K trisodium;(8Z)-7-oxo-8-[(4-sulfonatonaphthalen-1-yl)hydrazinylidene]naphthalene-1,3-disulfonate Chemical compound [Na+].[Na+].[Na+].C1=CC=C2C(N\N=C3/C(=O)C=CC=4C=C(C=C(C=43)S([O-])(=O)=O)S(=O)(=O)[O-])=CC=C(S([O-])(=O)=O)C2=C1 IVNZBWNBYXERPK-DZGBHZPSSA-K 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
KAISERLICHESIMPERIAL
PATENTAMT.PATENT OFFICE.
Physiologische Versuche mit den Estern der p-Acetamidophenoxylessigsäure haben ergeben, dafs dieselben zwar stark antipyretische Eigenschaften besitzen, zugleich aber von schädlichen Nebenwirkungen begleitet sind, indem sie in solchem Mafse Uebelkeit erzeugen und brechenerregend wirken, dafs ihre Anwendung für medizinische Zwecke ausgeschlossen ist.Physiological tests with the esters of p-acetamidophenoxyacetic acid have shown that they have strong antipyretic properties, but at the same time are harmful Side effects are accompanied by producing nausea to such an extent and have an emetic effect that their use for medical purposes is excluded.
Die vorliegende Erfindung beruht nun auf der Annahme, dafs die geschilderten lästigen Nebenwirkungen die Folge der Anhäufung des SauerstoffesThe present invention is based on the assumption that the above are bothersome Side effects result from the accumulation of oxygen
CH2-CO O —CH 2 -CO O -
1
O 1
O
im Molecül sind und dafs diese durch Einführung positiver Gruppen, wie z. B. des Ammoniakrestes — N H2 , beseitigt werden möchten. Zugleich war Erfinder der Ansicht, dafs die Amidgruppe als solche sowohl als ganz besonders in ihrer Stellung zum Phenol-are in the molecule and that these by introducing positive groups, such as B. the ammonia residue - NH 2 , want to be eliminated. At the same time, the inventor was of the opinion that the amide group as such as well as its position in relation to the phenol
CH2COGC2H5 CH 2 COGC 2 H 5
+ NH3 =+ NH 3 =
N-.COH CH3 N-.COH CH 3
in das zugehörige Amid über.into the corresponding amide.
Das entstandene p-Acetamidophenoxylacetamid besitzt in der That die erwarteten Eigenschaften, indem es vollständig ungiftig, d. h. ohne lästige Nebenwirkungen ist und prompt antipyretisch wirkt.The resulting p-acetamidophenoxylacetamide actually has the expected properties, by being completely non-toxic, d. H. has no annoying side effects and has an antipyretic effect promptly.
rest von günstiger Wirkung auf das Nerven-' system sein müsse.rest of a beneficial effect on the nervous' system.
Aus diesen Gründen führte Erfinder die Ester der p-Acetamidophenoxylessigsäure durch geJ eignete Behandlung mit Ammoniak entsprechend der GleichungFor these reasons, inventors led the esters of p-Acetamidophenoxylessigsäure by J ge suitable treatment with ammonia according to the equation
CH2 CONH2 OCH 2 CONH 2 O
C2H5OHC 2 H 5 OH
N-.COH
I
CH N-.COH
I.
CH
Beschreibung der Darstellung. .
Das Ausgangsmaterial ist die p-Nitrophenoxylessigsäure, welche von Fritzsche (J. f.
pr. Chem. [2], 20, 290) beschrieben wurde und bei 1830C. schmilzt. -■ "./.·.Description of the representation. .
The starting material is the p-Nitrophenoxylessigsäure which by Fritzsche (f. J. pr. Chem. [2], 20, 290) has been described, and melts at 183 0 C.. - ■ "./.·.
I.I.
ι. Gewinnung der Ester der p-Nitrophenoxylessigsäure. ι. Obtaining the esters of p-nitrophenoxyacetic acid.
Die Ester lassen sich leicht nach den gebräuchlichen Methoden darstellen:The esters can easily be prepared using the usual methods:
a) 2 Theile p-Nitrophenoxylessigsäure werden in einem Gemisch von 2 Theilen Schwefelsäure mit 6 Theilen Methyl-, Aethyl- oder Propylalkohol gelöst und 20 bis 30 Minuten am Rückflufskühler gekocht. Die gewonnene alkoholische Lösung wird alsdann in die fünfbis sechsfache Menge Wassers unter Umrühren eingegossen, wobei sich der betreffende Ester in kleinen Krystallen abscheidet. Die Krystalle werden abgesaugt und aus Alkohol umgelöst.a) 2 parts of p-nitrophenoxyacetic acid become in a mixture of 2 parts sulfuric acid with 6 parts methyl, ethyl or Dissolved propyl alcohol and refluxed for 20 to 30 minutes. The won The alcoholic solution is then poured into five to six times the amount of water while stirring poured in, the ester in question separating out in small crystals. The crystals are sucked off and redissolved from alcohol.
b) Man löst die p-Nitrophenoxylessigsäure in heifsem Alkohol und leitet in die heifse Lösung bis zur Sättigung gasförmige Salzsäure ein. Die überschüssige Salzsäure wird verjagt und die alkoholische Lösung wie unter a) be-. handelt.b) The p-nitrophenoxyacetic acid is dissolved in hot alcohol and passed into the hot alcohol Solution in gaseous hydrochloric acid until saturation. The excess hydrochloric acid is chased away and the alcoholic solution as under a) loading. acts.
p-Nitrophenoxylessigsäuremethylester schmilzt bei 100 bis 1010C, p-Nitrophenoxylessigsäureäthylester bei 73 bis 740 C. und p-Nitrophenoxylessigsäurepropylester bei 75 bis j6° C. p-Nitrophenoxylessigsäuremethylester melts at 100-101 0 C, p-Nitrophenoxylessigsäureäthylester at 73-74 0 C. and p-Nitrophenoxylessigsäurepropylester at 75 to j6 ° C.
2. Darstellung der p-Acetamidophenoxylessigsäureester. 2. Preparation of the p-acetamidophenoxyacetic acid esters.
Die p-Nitrophenoxylessigsäureester werden behufs Reduction in der fünf- bis sechsfachen Gewichtsmenge Eisessig gelöst, die berechnete Menge granulirtes Zinn zugegeben und in einem geräumigen Kolben am Rückflufskühler so lange erwärmt, bis die Reaction eintritt. Sobald diese beendet ist, wird zur Acetylirung der entstandenen Amidogruppe 6 bis 8 Stunden am Rückflufskühler gekocht und alsdann der bei Weitem gröfste Theil des Eisessigs abdestillirt. Der Rückstand wird in viel siedendes Wasser gegossen und die Lösung von dem abgeschiedenen Zinnhydroxyd durch Filtriren im Heifswassertrichter getrennt. Wendet man 5 Gewichtstheile Eisessig und 1 Gewichtstheil Essigsäureanhydrid an, so ist die Acetylirung nach vollendeter Reaction vollendet und man kann sofort den Eisessig abdestilliren. Die Ester werden aus der heifsen Lösung mit Natriumacetat ausgesalzen und der entsprechende Niederschlag zweimal aus siedendem Wasser umkrystallisirt.The p-nitrophenoxy acetic acid esters are for the purpose of reduction dissolved in five to six times the amount by weight of glacial acetic acid, the calculated one A quantity of granulated tin was added and placed in a large flask on the reflux condenser heated until the reaction occurs. As soon as this has ended, acetylation takes place the resulting amido group is boiled for 6 to 8 hours on the reflux condenser and then the by far the largest part of the glacial acetic acid is distilled off. The residue turns into a lot of boiling Poured water and the solution of the deposited tin hydroxide by filtration separated in the hot water funnel. If 5 parts by weight of glacial acetic acid and 1 part by weight are used Acetic anhydride, the acetylation is complete after the reaction is complete, and one can immediately distill off the glacial acetic acid. The esters are from the hot solution with Sodium acetate salted out and the corresponding precipitate twice from boiling water recrystallized.
ρ - Acetamidophenoxylessigsäuremethylester schmilzt bei 129 bis 1300C, p-Acetamidophenoxylessigsäureäthylester bei 103 bis 1040C, ρ - Acetamidophenoxylessigsäurepropylester bei 66 bis 68° C.ρ - Acetamidophenoxylessigsäuremethylester melts at 129-130 0 C, p-Acetamidophenoxylessigsäureäthylester at 103 to 104 0 C, ρ - Acetamidophenoxylessigsäurepropylester at 66 to 68 ° C.
3. Darstellung des Amids.
Zur Ueberführung der Ester der ρ -Acetamidophenoxylessigsäure in das zugehörige
Amid übergiefst man in einem Erlenmeyerschen Kolben die Ester mit der drei- bis vierfachen Gewichtsmenge 25 bis 30 proc. wässerigen
Ammoniaks und' schüttelt so lange, bis das angeschüttelte Pulver einen steifen Brei bildet.
Zur Vollendung der Reaction läfst man 1 Stunde stehen, saugt ab und krystallisirt aus siedendem
Wasser um.3. Representation of the amide.
To convert the esters of ρ-acetamidophenoxylacetic acid into the associated amide, pour the esters three to four times the weight of 25 to 30 percent in an Erlenmeyer flask. aqueous ammonia and 'shake until the powder is shaken into a stiff paste. To complete the reaction, the mixture is left to stand for 1 hour, suctioned off, and crystallized from boiling water.
II.II.
Zu demselben p-Acetamidophenoxylacetamid gelangt man aber auch, wenn man genau in derselben Weise, wie vorher die p-Acetamidophenoxylessigsäureester, die p-Nitrophenoxylessigsäureester durch Schütteln mit cone, wässerigem Ammoniak in das p-Nitrophenoxylacetamid (Schmelzpunkt 158 bis i6o° C.) überführt und dies genau, wie vorher die Ester, reducirt und acetylirt:But the same p-acetamidophenoxylacetamide can also be reached if one goes exactly in in the same way as before the p-acetamidophenoxyacetic acid esters, the p-nitrophenoxyacetic acid esters by shaking with cone, aqueous ammonia into the p-nitrophenoxylacetamide (Melting point 158 to 160 ° C.) transferred and this, just like the esters before, reduced and acetylated:
CH2COOC2H6 CH 2 COOC 2 H 6
CH2CONH2 CH 2 CONH 2
I
O I.
O
NO,NO,
+ C2H5 OH;+ C 2 H 5 OH;
CH2 CONH2 CH 2 CONH 2
2.2.
CH2 C O NH2 CH 2 CO NH 2
NO9 NO 9
+ 2 H2 O;+ 2 H 2 O ;
NHNH
CH2 CONH2 CH 2 CONH 2
NHNH
CH3 CH 3
CECE
CH2 CONH2 CH 2 CONH 2
I ·
O
II ·
O
I.
+ CHCOOH. + CHCOOH.
N: COHN: COH
I
CH,I.
CH,
Eigenschaften des ρ-Acetamidophenoxylacetamids. Properties of ρ-acetamidophenoxylacetamide.
Das reine p-Acetamidophenoxylacetamid zeigt keinen ganz scharfen Schmelzpunkt, sondern beginnt bei 2020C. zu sintern und schmelzen und ist bei 208 ° C. eine wasserhelle klare Flüssigkeit. Es bildet nadeiförmige, reinweifse Krystalle von etwas bitterlichem Geschmack. Es ist wenig in kaltem, leicht in siedendem Wasser und kaltem Alkohol löslich, fast unlöslich in Aether und Benzol. Es besitzt ferner die Eigenschaft, ein Molecül Chloral zu addiren (s. Patent Nr. 96493).The pure p-Acetamidophenoxylacetamid shows no very sharp melting point, but starts to sinter at 202 0 C. and melt at 208 ° C. and is a water-white clear liquid. It forms needle-shaped, pure white crystals with a somewhat bitter taste. It is sparingly soluble in cold, easily soluble in boiling water and cold alcohol, and almost insoluble in ether and benzene. It also has the property of adding a molecule of chloral (see patent no. 96493).
Eine Probe des Acetamidophenoxylacetamids mit ι ecm cone. Salzsäure gekocht und ι ο ecm destillirtem Wasser verdünnt giebt auf Zusatz von 5 bis 6 Tropfen gesättigter Phenollösung und ι bis 2 Tropfen wässeriger Chromsäurelösung ι : 4 Purpurrothfärbung, welche bei vorsichtigem Ueberschichten mit cone. Ammoniak an der Berührungsfläche in schön Grünblau umschlägt.A sample of Acetamidophenoxylacetamids with ι ecm cone. Hydrochloric acid boiled and ι ο ecm Diluted with distilled water, 5 to 6 drops of saturated phenol solution are added and ι to 2 drops of aqueous chromic acid solution ι: 4 purple-red color, which at careful overlaying with cone. Ammonia on the contact surface in a beautiful green-blue turns over.
Claims (1)
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE96492C true DE96492C (en) |
Family
ID=367630
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DENDAT96492D Active DE96492C (en) |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE96492C (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2426885A (en) * | 1942-10-09 | 1947-09-02 | Lowell B Kilgore | N-substituted alpha-oxyacetamides and insect combating compositions |
-
0
- DE DENDAT96492D patent/DE96492C/de active Active
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2426885A (en) * | 1942-10-09 | 1947-09-02 | Lowell B Kilgore | N-substituted alpha-oxyacetamides and insect combating compositions |
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