CH329572A - Process for the preparation of basic amides - Google Patents
Process for the preparation of basic amidesInfo
- Publication number
- CH329572A CH329572A CH329572DA CH329572A CH 329572 A CH329572 A CH 329572A CH 329572D A CH329572D A CH 329572DA CH 329572 A CH329572 A CH 329572A
- Authority
- CH
- Switzerland
- Prior art keywords
- acid
- preparation
- formula
- substituted
- basic amides
- Prior art date
Links
- 150000001408 amides Chemical class 0.000 title claims description 5
- 238000000034 method Methods 0.000 title claims description 5
- 238000002360 preparation method Methods 0.000 title claims description 4
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 3
- 229930195729 fatty acid Natural products 0.000 claims description 3
- 239000000194 fatty acid Substances 0.000 claims description 3
- 150000004665 fatty acids Chemical class 0.000 claims description 3
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical group [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- SGXDXUYKISDCAZ-UHFFFAOYSA-N N,N-diethylglycine Chemical compound CCN(CC)CC(O)=O SGXDXUYKISDCAZ-UHFFFAOYSA-N 0.000 description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 229940051881 anilide analgesics and antipyretics Drugs 0.000 description 3
- UFFBMTHBGFGIHF-UHFFFAOYSA-N 2,6-dimethylaniline Chemical compound CC1=CC=CC(C)=C1N UFFBMTHBGFGIHF-UHFFFAOYSA-N 0.000 description 2
- IPXNXMNCBXHYLQ-UHFFFAOYSA-N 2-pyrrolidin-1-ylacetic acid Chemical compound OC(=O)CN1CCCC1 IPXNXMNCBXHYLQ-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- FFDGPVCHZBVARC-UHFFFAOYSA-N N,N-dimethylglycine Chemical compound CN(C)CC(O)=O FFDGPVCHZBVARC-UHFFFAOYSA-N 0.000 description 2
- -1 aliphatic amino acids Chemical class 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- FBBDOOHMGLLEGJ-UHFFFAOYSA-N methane;hydrochloride Chemical compound C.Cl FBBDOOHMGLLEGJ-UHFFFAOYSA-N 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- QNWMFJDRMZWZNN-UHFFFAOYSA-N 2,6-dimethylaniline;hydron;chloride Chemical compound Cl.CC1=CC=CC(C)=C1N QNWMFJDRMZWZNN-UHFFFAOYSA-N 0.000 description 1
- HQDXZMGISBZJCQ-UHFFFAOYSA-N 2-(benzylamino)hexanoic acid Chemical compound CCCCC(C(O)=O)NCC1=CC=CC=C1 HQDXZMGISBZJCQ-UHFFFAOYSA-N 0.000 description 1
- RRWZZMHRVSMLCT-UHFFFAOYSA-N 2-(butylazaniumyl)acetate Chemical compound CCCCNCC(O)=O RRWZZMHRVSMLCT-UHFFFAOYSA-N 0.000 description 1
- WFNLHDJJZSJARK-UHFFFAOYSA-N 2-chloro-6-methylaniline Chemical compound CC1=CC=CC(Cl)=C1N WFNLHDJJZSJARK-UHFFFAOYSA-N 0.000 description 1
- CDGWFKQTRDZBTA-UHFFFAOYSA-N 2-chloro-6-methylaniline;hydrochloride Chemical compound Cl.CC1=CC=CC(Cl)=C1N CDGWFKQTRDZBTA-UHFFFAOYSA-N 0.000 description 1
- VRDBIJCCXDEZJN-UHFFFAOYSA-N 2-piperidin-1-ylacetic acid Chemical compound OC(=O)CN1CCCCC1 VRDBIJCCXDEZJN-UHFFFAOYSA-N 0.000 description 1
- 244000309494 Bipolaris glycines Species 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical class CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 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
- C07D207/04—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 no double bonds between ring members or between ring members and non-ring members
- C07D207/08—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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
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Verfahren zur Herstellung basischer Amide b Gegenstand des Patentes bildet ein Verfahren zur Herstellung basischer Amide der Formel Ar -NII-CO-R Am, in welcher Ar ein mindestens in 2- und 6-Stel- lung dLtrch Substituenten erster Ordnung substituiertes Phenylradikal, R einen niederen Alkylenrest und Am eine substituierte Amino- gruppe bedeutet. Verbindungen dieser Art sowie ihre lokalanästhetische Wirkung sind zum Teil schon bekannt (vgl. z. B.
USA-Patent Nr. 2441.498, Brit. Patent Nr. 705460).
Das erfindungsgemässe Verfahren ist. da- durch gekennzeichnet, dass man auf ein Phos- phazo-anilid der Formel Ar-N-P-NI3-Ar eine basisch substituierte Fettsäure der Formel 1IOOC-R-Am einwirken lässt.
Die Umsetzung erfolgt vorzugsweise in einem inerten L0slulgs- bzw. Verdünnungsmittel und bei erhöhter Temperatur. Die Phos- phazo-anilide können durch Reaktion eines Anilins mit einem Phosphortrihalogenid erhalten werden.
Dass die Umsetzung der basisch substituierten Fettsäuren mit den Phosphazo-anili- cien zu den gewünschten basischen. Amiden führen würde, war nicht vorauszusehen. II. W. Crimiuel et a1., beschrieben in Jour. Am. Chefin. Soe. 68, S. 539 usf. (1.946), die Umset- zung von aliphatis & ##Il; -aromatischen und heterocyclisehen Säuren mit Phösphazo-anili- den, die allerdings zu den erwarteten Acyl- anili.nen führten.
Die Autoren betonen aber in ihrer Arbeit, dass aliphatische Aminosäu- ren, wie z. B. Glycin und Alanin, sieh nicht mit Phospliazo-aniliden umsetzen liessen.
Beispiel 1 283 g 2-Chlor-6-methyl-anilin in 400 cm3 absolutem Benzol werden tropfenweise unter Aussenkühlung mit einer Lösung von 55 g Phosphortrichlorid in 150 em3 absolutem Benzol versetzt. Man filtriert anschliessend das , -tusoefallene 2-Chlor-6-methyl-anilin-hydro- chlorid ab und verdampft das Filtrat zur Trockne. Der Rückstand, bestehend aus dem 2-Chlor - 6 -methyl-phenyl-phosphazo-2-chlor-6- methyl-anilid, stellt eine bräunliche, halb kristalline Masse dar.
Diese wird ohne Reinigung in 300 em3 Chloroform gelöst, mit 65g Di- äthylaminoessigsäure versetzt. und das Ganze acht Stunden zum Sieden erhitzt. Anschlie- ssend gibt man Äther zu, schüttelt einige Male mit verdünnter Natronlauge aus und verdampft das Lösungsmittel. Den Rückstand löst man in verdünnter Salzsäure, gibt Kohle zu, filtriert und macht mit. Natronlauge alkalisch. Das sieh ausscheidende Öl wird in Äther aufgenommen, die ätherische Lösung nach dem Trocknen verdampft und der Rückstand im Iloclivakuum destilliert.
Man erhält das Di- ätliyla.ininoessig- äure-2-elilor-6-metliyl-anilid
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als farbloses Öl, das unter 0,05 mm bei 125" C siedet. Dieses Öl erstarrt nach einiger Zeit zu Kristallen, die bei 52--53 C schmelzen. Die Ausbeute beträgt 70 g.
In gleicher Weise wie hier für Diäthyl- aminoessigsäure beschrieben kann man beispielsweise Dimethylaminoessigsäure, ri-Pro- pylaminoessigsäure, n-Butylaminoessigsäure, Butylbenzylaminoessigsäure, Pyrrolidinoessig- säure, Piperidinoessigsäure und entsprechend substituierte Propion- und Buttersäuren zur L?rnsetzung bringen.
Beispiel 2 242 g 2,6-Dimethy 1-anilin in 600 cm3 absolutem Benzol werden unter Aussenkühlung und Rühren mit 55 g Phosphortrichlorid in 150 ein absolutem Benzol tropfenweise ver- setzt. Nach fünf Stunden wird das ausgefallene 2,6-Dimethyl-anilin-hydrochlorid abge- sauugt und das Filtrat eingedampft. Der Rückstand wird, wie in Beispiel 1 angegeben, mit 65g Diäthy laminoessigsäure zur Reaktion gebracht. Die Aufarbeitung erfolgt gleich wie in Beispiel 1 beschrieben.
Man erhält 126 g (das sind etwa 70 % d. Th.) Diäthy laininoessigsäur e- 2,6-dimetliy 1-anilid, das unter 0,04 mm bei 135 C siedet.
An. Stelle des 2,6-Dimethyl-anilins kann auch ein anderes substituiertes Anilin zur Umsetzung gebracht werden, z. B. 2,4,6-Tri- metlit-l-anilin (lIesidin), und an Stelle von 1)iätlivlaminoessigsäure, z. B. Pyrrolidino- essigsäure u. a. m.
In gleicher Weise wie in den Beispielen beschrieben lassen sich die folgenden basischen Amide der Formel
EMI2.55
herstellen:
EMI2.56
RR, R3 AM Schmelzpunkt C Hydrochlorid -C113 -C113 -C112 -N\ H I 198-199 C113\ -C113 -C113 -C112 -N/ H i 200-202 CH C113\ -C113 -C113 -CH- -N H ( 248-249 C113 C113/ C113\ -C113 -CL -C112 -N H i 228-230 C113/
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EMI3.1
R, R3 Am Schmelzpunkt C Hydrochlorid -C113 -CL -C112 1 @ H 194-196 CH3@ -C113 -CL -CH- -N/ H 244-246 C113 C113 -CL -CL -C112 - N H 220,5-221,5
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Process for the preparation of basic amides b The subject of the patent is a process for the preparation of basic amides of the formula Ar -NII-CO-R Am, in which Ar is a phenyl radical which is substituted at least in the 2- and 6-position dLtrch substituents of the first order, R a is a lower alkylene radical and Am is a substituted amino group. Compounds of this type as well as their local anesthetic effect are already known in some cases (see e.g.
U.S. Patent No. 2441,498, Brit. Patent No. 705460).
The inventive method is. characterized in that a phosphazo-anilide of the formula Ar-N-P-NI3-Ar is allowed to act on a base-substituted fatty acid of the formula 10OC-R-Am.
The reaction is preferably carried out in an inert solvent or diluent and at an elevated temperature. The phosphazo-anilides can be obtained by reacting an aniline with a phosphorus trihalide.
That the conversion of the basic substituted fatty acids with the phosphazo-anilicien to the desired basic. Amiden was unpredictable. II. W. Crimiuel et al., Described in Jour. At the. Boss. Soe. 68, p. 539 etc. (1.946), the implementation of aliphatis &##Il; -aromatic and heterocyclic acids with phösphazo-anilides, which, however, led to the expected acyl-anilines.
However, the authors emphasize in their work that aliphatic amino acids such as B. glycine and alanine, see not allowed to react with phospliazo-anilides.
Example 1 283 g of 2-chloro-6-methyl-aniline in 400 cm3 of absolute benzene are added dropwise with external cooling with a solution of 55 g of phosphorus trichloride in 150 cm3 of absolute benzene. The 2-chloro-6-methyl-aniline hydrochloride which has precipitated is then filtered off and the filtrate is evaporated to dryness. The residue, consisting of the 2-chloro-6-methyl-phenyl-phosphazo-2-chloro-6-methyl-anilide, is a brownish, semi-crystalline mass.
This is dissolved in 300 cubic meters of chloroform without purification, and 65 g of diethylaminoacetic acid are added. and boiled the whole thing for eight hours. Then ether is added, shaken out a few times with dilute sodium hydroxide solution and the solvent is evaporated. Dissolve the residue in dilute hydrochloric acid, add charcoal, filter and take part. Caustic soda alkaline. The oil which separates out is taken up in ether, the ethereal solution is evaporated after drying and the residue is distilled in an Iloclivakuum.
The diethyl amino acetic acid 2-elilor-6-methyl anilide is obtained
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as a colorless oil that boils below 0.05 mm at 125 "C. This oil solidifies after a while to form crystals which melt at 52-53 C. The yield is 70 g.
In the same way as described here for diethylaminoacetic acid, for example, dimethylaminoacetic acid, ri-propylaminoacetic acid, n-butylaminoacetic acid, butylbenzylaminoacetic acid, pyrrolidinoacetic acid, piperidinoacetic acid and correspondingly substituted propionic and butyric acids can be dissolved.
Example 2 To 242 g of 2,6-dimethyl-1-aniline in 600 cm3 of absolute benzene, 55 g of phosphorus trichloride in 150 of an absolute benzene are added dropwise with external cooling and stirring. After five hours, the precipitated 2,6-dimethyl aniline hydrochloride is suctioned off and the filtrate is evaporated. As indicated in Example 1, the residue is reacted with 65g diethylaminoacetic acid. Working up is carried out in the same way as described in Example 1.
126 g (about 70% of theory) diethylaininoacetic acid 2,6-dimethyl 1-anilide which boils below 0.04 mm at 135 ° C. are obtained.
On. Instead of the 2,6-dimethyl aniline, another substituted aniline can also be reacted, e.g. B. 2,4,6-tri-metlit-l-aniline (lesidin), and instead of 1) iätlivlaminoacetic acid, z. B. pyrrolidino acetic acid u. a. m.
In the same way as described in the examples, the following basic amides of the formula
EMI2.55
produce:
EMI2.56
RR, R3 AM melting point C hydrochloride -C113 -C113 -C112 -N \ HI 198-199 C113 \ -C113 -C113 -C112 -N / H i 200-202 CH C113 \ -C113 -C113 -CH- -NH (248 -249 C113 C113 / C113 \ -C113 -CL -C112 -NH i 228-230 C113 /
<Desc / Clms Page number 3>
EMI3.1
R, R3 At melting point C hydrochloride -C113 -CL -C112 1 @ H 194-196 CH3 @ -C113 -CL -CH- -N / H 244-246 C113 C113 -CL -CL -C112 - NH 220.5-221 , 5
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH329572T | 1954-07-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH329572A true CH329572A (en) | 1958-04-30 |
Family
ID=4501384
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH329572D CH329572A (en) | 1954-07-29 | 1954-07-29 | Process for the preparation of basic amides |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH329572A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2532306A1 (en) * | 1982-08-27 | 1984-03-02 | Pharmaton Sa | BASIC ACETANILIDES, PROCESS FOR THEIR PREPARATION AND MEDICAMENTS CONTAINING THE SAME |
-
1954
- 1954-07-29 CH CH329572D patent/CH329572A/en unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2532306A1 (en) * | 1982-08-27 | 1984-03-02 | Pharmaton Sa | BASIC ACETANILIDES, PROCESS FOR THEIR PREPARATION AND MEDICAMENTS CONTAINING THE SAME |
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