DE518208C - Process for the preparation of acylaminobenzolestibic acids - Google Patents
Process for the preparation of acylaminobenzolestibic acidsInfo
- Publication number
- DE518208C DE518208C DEI38395D DEI0038395D DE518208C DE 518208 C DE518208 C DE 518208C DE I38395 D DEI38395 D DE I38395D DE I0038395 D DEI0038395 D DE I0038395D DE 518208 C DE518208 C DE 518208C
- Authority
- DE
- Germany
- Prior art keywords
- acid
- stibic
- acids
- hydrogen
- 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.)
- Expired
Links
- 239000002253 acid Substances 0.000 title claims description 25
- 150000007513 acids Chemical class 0.000 title claims description 6
- 238000000034 method Methods 0.000 title claims description 3
- 238000002360 preparation method Methods 0.000 title claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims 4
- 239000001257 hydrogen Substances 0.000 claims 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
- 150000002431 hydrogen Chemical class 0.000 claims 2
- 125000004442 acylamino group Chemical group 0.000 claims 1
- 125000003277 amino group Chemical group 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- ADCOVFLJGNWWNZ-UHFFFAOYSA-N antimony trioxide Chemical compound O=[Sb]O[Sb]=O ADCOVFLJGNWWNZ-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- -1 4-acetylamino-2-methyl-i-aminobenzene hydrochloride Chemical compound 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 2
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- KJFMBFZCATUALV-UHFFFAOYSA-N phenolphthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2C(=O)O1 KJFMBFZCATUALV-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 208000037972 tropical disease Diseases 0.000 description 2
- XTTIQGSLJBWVIV-UHFFFAOYSA-N 2-methyl-4-nitroaniline Chemical compound CC1=CC([N+]([O-])=O)=CC=C1N XTTIQGSLJBWVIV-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000006193 diazotization reaction Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- ACLVOBFSJRPZQD-UHFFFAOYSA-N n-(2-methoxy-5-methyl-4-nitrophenyl)acetamide Chemical compound COC1=CC([N+]([O-])=O)=C(C)C=C1NC(C)=O ACLVOBFSJRPZQD-UHFFFAOYSA-N 0.000 description 1
- SJWQCBCAGCEWCV-UHFFFAOYSA-N n-(3-amino-4-methoxyphenyl)acetamide Chemical compound COC1=CC=C(NC(C)=O)C=C1N SJWQCBCAGCEWCV-UHFFFAOYSA-N 0.000 description 1
- ROKKABNPZRSHHY-UHFFFAOYSA-N n-(4-amino-2,5-dichlorophenyl)acetamide Chemical compound CC(=O)NC1=CC(Cl)=C(N)C=C1Cl ROKKABNPZRSHHY-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Substances [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/90—Antimony compounds
- C07F9/92—Aromatic compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Verfahren zur Herstellung von Acylaminobenzolstibinsäuren Es wurde gefunden, daß bei aromatischen Stibinsäuren die Einführung eines Substituenten in o-Stellung zum Stibinsäurerest ganz allgemein eine mehr oder weniger ausgeprägte perorale Wirkung bei Trypanosomenerkrankungen und anderen Tropenkrankheiten bedingt. Dieser Effekt ist um so höher zu bewerten, als eine wirksame Bekämpfung der Tropenkrankheiten nur möglich ist, wenn ein Mittel gefunden wird, das dem Patienten selbst in die Hand gegeben werden kann, so daß er nicht zu jeder einzelnen Applikation auf ärztliche Hilfe (z. B. intravenöse Injektion) angewiesen ist. Die Herstellung geschieht in an sich bekannter Weise.Process for the preparation of acylaminobenzenesibinic acids It has been found that the introduction of a substituent in aromatic stibic acids o-position to the stibic acid residue quite generally a more or less pronounced one Peroral effect in trypanosomal diseases and other tropical diseases conditional. This effect is all the more highly valued as an effective fight against tropical diseases is only possible if a remedy is found that can help the patient himself Hand can be given, so that he does not have to medical for every single application Assistance (e.g. intravenous injection) is required. The production takes place in in a manner known per se.
Diese durch die Einführung des Substituenten in o-Stellung bedingte Wirkung ist überraschend, da die bisher gebräuchlichen Stibinsäuren, wie p-Acetylaminobenzolstibinsäure, p-Aminobenzolstibinsäure, .3-Chlor-4-acetylaininobenzolstibinsäure, bei peroraler Verabreichung keine Wirkung zu entfalten vermögen.This caused by the introduction of the substituent in the o-position The effect is surprising because the stibic acids commonly used up to now, such as p-acetylaminobenzolestibic acid, p-aminobenzenestibic acid, 3-chloro-4-acetylaininobenzenostibic acid, for peroral Administration is unable to develop any effect.
Beispiele i. 40 g 4-Acetylamino-2-methyl-i-aminobenzolhydrochlorid werden in Zoo ccm Wasser gelöst und nach Zusatz von 32 ccm konz. Salzsäure dianotiert. Die klare Diazolösung wird bei 15 bis 251 in eine Mischung von 30 g Antimontr ioxyd, 6o ccm Natronlauge (4o° Be), $o g Glycerin, Zoo ccm Wasser und 2 g Kupfer langsam eingerührt, wobei unter lebhafter Stickstoffentwicklung die Umsetzung erfolgt. Wenn die Mischung nicht mehr kuppelt, wird mit Salzsäure bis zur schwach alkalischen Reaktion gegenüber Phenolphthalein abgestumpft, mit Kohlensäure gesättigt und klar filtriert. Die Lösung wird mit Salzsäure angesäuert, -die ausfallende Stibinsäure abgesaugt und mit ,Wasser ausgewaschen. Zur Reinigung löst man in Methylalkohol, saugt vom Ungelösten ab und fällt mit Äther. Man erhält so die 4-Acetylamino-2-methy lbenzol-i-stibinsäure als ein weißes, in verdünnten Alkalien leicht lösliches Pulver, das beim Erhitzen verkohlt, ohne zu schmelzen.Examples i. 40 g of 4-acetylamino-2-methyl-i-aminobenzene hydrochloride are dissolved in zoo ccm of water and, after the addition of 32 ccm of conc. Dianotized hydrochloric acid. The clear diazo solution is ioxyd at 15 to 251 in a mixture of 30 g Antimontr, 6o cc of sodium hydroxide solution (4o ° Be), $ og glycerol, zoo cc of water and 2 g of copper stirred slowly, keeping the reaction is carried out with vigorous evolution of nitrogen. When the mixture no longer couples, it is blunted with hydrochloric acid until it reacts slightly alkaline to phenolphthalein, saturated with carbonic acid and filtered until clear. The solution is acidified with hydrochloric acid, the precipitated stibic acid is suctioned off and washed out with water. To clean it, one dissolves in methyl alcohol, sucks off the undissolved material and falls with ether. 4-Acetylamino-2-methylbenzene-i-stibic acid is obtained in this way as a white powder which is easily soluble in dilute alkalis and which carbonizes on heating without melting.
Geht man von der entsprechenden Valeryl-oder Benzoylverbindung aus, so erhält man als Endprodukt die 4-Valerylamino-2-methylbenzol-i-stibinsäure bzw. die 4-Benzoylamino-2-inethylbenzol-i-stibinsäure.If one proceeds from the corresponding valeryl or benzoyl compound, the end product obtained is 4-valerylamino-2-methylbenzene-i-stibic acid or 4-benzoylamino-2-ynethylbenzene-i-stibic acid.
2. 2S g 4-Amino-2-methylbenzol-i-stibinsäure, hergestellt durch Umsetzen von dianotiertem 4-N itro-2-methyl-i-aminobenzol mit Antimonit und Reduktion der erhaltenen Nitrosäure, werden als Natriumsalz in i 5o ccm Wasser gelöst. Unter Rühren läßt man bei Zimmertemperatur 15 g Essigsäureanhydrid zufließen und rührt, bis die Temperatur wieder gefallen ist. Dann setzt man Salzsäure zu, bis die Lösung kongosauer ist, saugt ab und reinigt die- 4-Acetylamino-2-methylbenzol-i-stibinsäure, wie in Beispiel i angegeben.2. 2½ g of 4-amino-2-methylbenzene-i-stibic acid, prepared by reaction of dianotated 4-nitro-2-methyl-i-aminobenzene with antimonite and reduction of the The nitro acid obtained are dissolved as the sodium salt in 150 cc of water. While stirring 15 g of acetic anhydride are left at room temperature flow in and stir until the temperature has dropped again. Then you add hydrochloric acid, until the solution is Congo acid, sucks off and purifies the 4-acetylamino-2-methylbenzene-i-stibic acid, as indicated in example i.
3. 44 g 4-Acetylamino-2,5-dichlor-i-aminobenzol werden mit der zur Diazotierung nötigen Menge Nitritlösung und Wasser in der Kugelmühle zu einem dünnen Brei vermahlen und durch Eingießen in 48 ccm Salzsäure und 300 ccm Eiswasser diazotiert. Die Diazolösung wird, wie in Beispiel i angegeben, mit Antimonit umgesetzt.3. 44 g of 4-acetylamino-2,5-dichloro-i-aminobenzene are ground to a thin paste with the amount of nitrite solution and water required for diazotization in a ball mill and diazotized by pouring into 48 cc of hydrochloric acid and 300 cc of ice water. The diazo solution is, as indicated in Example i, reacted with antimonite.
Zur Reinigung wird die rohe 4-Acetylamino-2,5-dichlorbenzol-i-stibinsäure in Methylalkohol suspendiert, mit wenig Ammoniaklösung in Lösung gebracht und mit Äther als Ammoniumsalz gefällt. Weißes, leicht in Wasser mit neutraler Reaktion lösliches Pulver.The crude 4-acetylamino-2,5-dichlorobenzene-i-stibic acid is used for purification suspended in methyl alcohol, brought into solution with a little ammonia solution and with Ether precipitated as the ammonium salt. White, easily in water with neutral reaction soluble powder.
4. 18 g 3-Acetylamino-6-methoxy-i-aminobenzol werden in der üblichen Weise diazotiert und mit einer Antimonitlösung aus 15 g Antimontrioxyd umgesetzt. Die Abtrennung und Reinigung der 3-Acetylamino-6-methoxybenzol-i-stibinsäure geschieht in ähnlicher Weise wie bei den -vorhergehenden Beispielen. Man kann zur Abtrennung auch die mit Kohlensäure gesättigte Lösung mit Natriumhydros.ulfzt .behandeln, das gebildete Stibinbenzol absaugen und mit Wasserstoffsuperoxyd wieder zur Stibinsäure oxydieren. Die Säure stellt ein fast weißes, in verdünnten Alkalien und Ammoniak spielend lösliches Pulver dar.4. 18 g of 3-acetylamino-6-methoxy-i-aminobenzene are in the usual Way diazotized and reacted with an antimonite solution of 15 g of antimony trioxide. The 3-acetylamino-6-methoxybenzene-i-stibic acid is separated off and purified in a similar way to the previous examples. One can go to separation also treat the solution saturated with carbonic acid with sodium hydrosulfite, the Suck off the stibinbenzene formed and return to stibic acid with hydrogen peroxide oxidize. The acid represents an almost white, in dilute alkalis and ammonia easily soluble powder.
5. 229 3-Glykolylamino-6-oxy-i-amiiiobenzolhydrochlorid, hergestellt durch Schmelzen von 3-Amino-6-oxy-i-nitrobenzol mit Glykolsäure unter nachfolgender Reduktion der Nitrogruppe, werden diazotiert und mit einer Antimonitlösung aus 15 g. Antimontrioxyd zur Umsetzung gebracht.5. 229 3-glycolylamino-6-oxy-i-amiiiobenzene hydrochloride, prepared by melting 3-amino-6-oxy-i-nitrobenzene with glycolic acid with subsequent reduction of the nitro group, are diazotized and treated with an antimonite solution of 15 g. Antimony trioxide brought to implementation.
Die 3-Glykolylamino-6-oxybenzol-i-stibinsäure ist ein weißes, in Alkalien leicht lösliches Pulver.The 3-glycolylamino-6-oxybenzene-i-stibic acid is a white, in alkalis easily soluble powder.
6.23,5 g 4-Acetylamino-3-metlioxy-6-tnethyl-i-aminobenzolhydrochlorid (aus 4-Acetylamino - 3 - methoxy - 6 - methyl- i -nitrobenzol durch katalytische Reduktion der Nitrogruppe hergestellt), werden, wie in den vorhergehenden Beispielen beschrieben, diazotiert und mit Antimonit umgesetzt. Die Reinigung der q. - Acetylamino - 3 - methoxy-6 -methylbenzoli-stibinsäure sowie die Darstellung ihrer Salze geschieht auch hier am besten durch Lösen in Methylalkohol und Fällen mit Äther.6.23.5 g of 4-acetylamino-3-metlioxy-6-methyl-i-aminobenzene hydrochloride (from 4-acetylamino - 3 - methoxy - 6 - methyl- i -nitrobenzene by catalytic Reduction of the nitro group), as in the previous examples described, diazotized and implemented with antimonite. The purification of the q. - acetylamino - 3 - methoxy-6-methylbenzenestibic acid and the representation of its salts happens here, too, it is best to dissolve it in methyl alcohol and precipitate it with ether.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEI38395D DE518208C (en) | 1929-06-15 | 1929-06-16 | Process for the preparation of acylaminobenzolestibic acids |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE349796X | 1929-06-15 | ||
| DEI38395D DE518208C (en) | 1929-06-15 | 1929-06-16 | Process for the preparation of acylaminobenzolestibic acids |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE518208C true DE518208C (en) | 1931-02-13 |
Family
ID=25828342
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEI38395D Expired DE518208C (en) | 1929-06-15 | 1929-06-16 | Process for the preparation of acylaminobenzolestibic acids |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE518208C (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE890960C (en) * | 1946-06-14 | 1953-09-24 | Hoffmann La Roche | Process for the preparation of a therapeutic agent consisting of an aromatic stibic acid |
-
1929
- 1929-06-16 DE DEI38395D patent/DE518208C/en not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE890960C (en) * | 1946-06-14 | 1953-09-24 | Hoffmann La Roche | Process for the preparation of a therapeutic agent consisting of an aromatic stibic acid |
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