DE1008308B - Process for the preparation of ª[(ª-dialkylamino-alkyl)-alkyl-amino]-phenyl-acetic acid isoamyl and -n-nonyl esters - Google Patents
Process for the preparation of ª[(ª-dialkylamino-alkyl)-alkyl-amino]-phenyl-acetic acid isoamyl and -n-nonyl estersInfo
- Publication number
- DE1008308B DE1008308B DEA17418A DEA0017418A DE1008308B DE 1008308 B DE1008308 B DE 1008308B DE A17418 A DEA17418 A DE A17418A DE A0017418 A DEA0017418 A DE A0017418A DE 1008308 B DE1008308 B DE 1008308B
- Authority
- DE
- Germany
- Prior art keywords
- alkyl
- amino
- isoamyl
- acetic acid
- nonyl
- 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
- 229960003424 phenylacetic acid Drugs 0.000 title claims description 3
- 239000003279 phenylacetic acid Substances 0.000 title claims description 3
- -1 n-nonyl Chemical group 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 150000003839 salts Chemical group 0.000 claims 2
- 150000007513 acids Chemical class 0.000 claims 1
- 125000003282 alkyl amino group Chemical group 0.000 claims 1
- 229910052500 inorganic mineral Inorganic materials 0.000 claims 1
- 239000011707 mineral Substances 0.000 claims 1
- GJQIMXVRFNLMTB-UHFFFAOYSA-N nonyl acetate Chemical compound CCCCCCCCCOC(C)=O GJQIMXVRFNLMTB-UHFFFAOYSA-N 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 description 2
- 150000004985 diamines Chemical class 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000003170 musculotropic effect Effects 0.000 description 2
- XQYZDYMELSJDRZ-UHFFFAOYSA-N papaverine Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- QWBQBUWZZBUFHN-UHFFFAOYSA-N 3-Methylbutyl phenylacetate Chemical compound CC(C)CCOC(=O)CC1=CC=CC=C1 QWBQBUWZZBUFHN-UHFFFAOYSA-N 0.000 description 1
- 229930008281 A03AD01 - Papaverine Natural products 0.000 description 1
- 238000007126 N-alkylation reaction Methods 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- ZGUNAGUHMKGQNY-UHFFFAOYSA-N alpha-phenylglycine Chemical class OC(=O)C(N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N benzyl-alpha-carboxylic acid Natural products OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- MLFHJEHSLIIPHL-UHFFFAOYSA-N isoamyl acetate Chemical compound CC(C)CCOC(C)=O MLFHJEHSLIIPHL-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- HVOYZOQVDYHUPF-UHFFFAOYSA-N n,n',n'-trimethylethane-1,2-diamine Chemical compound CNCCN(C)C HVOYZOQVDYHUPF-UHFFFAOYSA-N 0.000 description 1
- QICYMLLAPDCBNZ-UHFFFAOYSA-N nonyl 2-phenylacetate Chemical compound CCCCCCCCCOC(=O)CC1=CC=CC=C1 QICYMLLAPDCBNZ-UHFFFAOYSA-N 0.000 description 1
- 229960001789 papaverine Drugs 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
DEUTSCHESGERMAN
Nach dem Verfahren der deutschen Patentschrift 842 206 sind a-[(jS-Dialkylamino-alkyl)-amino]-phenylessigsäureester bekannt, von denen sich der <z-[(/5-Diäthylaminoäthyl) - amino] - phenyl - essigsaure - isoamylester der FormelAccording to the method of German Patent 842 206, a - [(jS-Dialkylamino-alkyl) -amino] -phenylacetic acid esters are obtained known, of which the <z - [(/ 5-diethylaminoethyl) - amino] - phenyl - acetic acid - isoamyl ester of formula
>—CH-COO-C5H11 (i)> —CH-COO-C 5 H 11 (i)
NH-CH2-CH2N (C2H5)2 NH-CH 2 -CH 2 N (C 2 H 5 ) 2
insbesondere durch eine muskulotrope, papaverinähnliche « Wirkung auszeichnet. Diese Verbindungen werden auf dem Wege der N-Alkylierung von a-Amino-phenyl-essigsäureestern erhalten, wobei die Umsetzung in Abwesenheit von Lösungsmitteln und unter Anwendung von Dialkylamino-alkylhalogeniden in Form ihrer Hydrohalogenide durchgeführt wird.especially through a musculotropic, papaverine-like " Effect. These compounds are obtained by means of the N-alkylation of α-amino-phenylacetic acid esters obtained, the reaction in the absence of solvents and with the use of Dialkylamino-alkyl halides is carried out in the form of their hydrohalides.
Es hat sich nun überraschenderweise herausgestellt, daß diese Verbindungen in der muskulotropen, papaverinähnlichen Wirkung von Verbindungen der allgemeinen Formel 1:It has now surprisingly been found that these compounds are in the musculotropic, papaverine-like Effect of compounds of general formula 1:
— CH-COO —R,- CH-COO —R,
R1-N-CH-CH2-NR 1 -N-CH-CH 2 -N
worin R und R1 = Methyl oder Äthyl, R2 = Wasserstoff oder Methyl und R3 = iso-Amyl oder n-Nonyl bedeuten, um etwa das vier- bis fünffache übertroffen werden.where R and R 1 = methyl or ethyl, R 2 = hydrogen or methyl and R 3 = iso-amyl or n-nonyl, are exceeded by about four to five times.
In der nachfolgenden Aufstellung werden die im Vergleich zu Papaverin, das gleich 1 gesetzt wurde, benötigten Mengen der neuen Verbindungen angegeben:In the following list, the required compared to papaverine, which was set equal to 1 Amounts of the new compounds indicated:
CHa CH a
N-CH9-CH9-NN-CH 9 -CH 9 -N
COO-C6H1 COO-C 6 H 1
-CH-CH
CH,CH,
N-CH2-CH2-NN-CH 2 -CH 2 -N
CH-COO-CH1 CH-COO-CH 1
C9H=C 9 H =
N- CH-CH9-NN-CH-CH 9 -N
-CH-COO-C9H19 -CH-COO-C 9 H 19
CH,CH,
CH,CH,
CH,CH,
CH5 CH 5
C9H5 C 9 H 5
C9H5 C 9 H 5
1 : 0,271: 0.27
1 : 0,191: 0.19
1 : 0,231: 0.23
Verfahren zur HerstellungMethod of manufacture
von α [(^Dialkylamino-alkyl)-alkyl-amino]-of α [(^ dialkylamino-alkyl) -alkyl-amino] -
phenyl-essigsäure-isoamyl- undphenylacetic acid isoamyl and
-n-nonylestern-n-nonyl esters
Anmelder:Applicant:
Asta-Werke A.-G.r Chemische Fabrik,
Brackwede (Westf.), Bielefelder Str. 83Asta-Werke A.-G. r chemical factory,
Brackwede (Westphalia), Bielefelder Str. 83
Dr. phil. nat. habil. Herbert Arnold, Bielefeld,Dr. phil. nat. habil. Herbert Arnold, Bielefeld,
und Dr. phil. Engelbert Kühas, Gadderbaum,and Dr. phil. Engelbert Kühas, Gadderbaum,
sind als Erfinder genannt wordenhave been named as inventors
a5 Diese Verbindungen sind auf dem vorgenannten Verfahrensweg erhältlich, sie werden jedoch bevorzugt durch Erhitzen der entsprechenden a-Halogen-phenyl-cssigsäureester mit entsprechend substituierten aliphatischen Diaminen in Abwesenheit von Lösungsmitteln gemäß folgendem Reaktionsschema: a 5 These compounds can be obtained by the above-mentioned process route, but they are preferably obtained by heating the corresponding a-halophenyl acetic acid ester with appropriately substituted aliphatic diamines in the absence of solvents according to the following reaction scheme:
CH- CO — OR,CH- CO - OR,
HalHal
R1-NH-CH(R2)-CH2-N(R)2 >1 R 1 -NH-CH (R 2 ) -CH 2 -N (R) 2 > 1
worin R, R1, R2 und R3 die oben angegebene Bedeutung haben, hergestellt.in which R, R 1 , R 2 and R 3 have the meanings given above.
Daß die Umsetzung zwischen den a-Halogen-phenylessigsäureestern und den substituierten Diaminen ausschließlich in der angegebenen Richtung verläuft und zur Bildung der a-[(/?-Dialkylaminoalkyl)-alkyl-amino]-phenyl-essigsäure-n-nonylester bzw. -isoamylester führt, war keineswegs zu erwarten. Im Gegenteil, auf Grund der Tatsache, daß Halogenatome in ct-Halogen-phenylessigsäureestern außerordentlich leicht beweglich sind, war vielmehr anzunehmen, daß die Reaktionspartner zumindest teilweise unter Bildung quaternärer Verbindungen reagieren würden.That the reaction between the a-halophenylacetic acid esters and the substituted diamines runs exclusively in the direction indicated and to Formation of the a - [(/? - Dialkylaminoalkyl) -alkyl-amino] -phenyl-acetic acid-n-nonyl ester or isoamyl ester was by no means to be expected. On the contrary, due to the Fact that halogen atoms in ct-halo-phenylacetic acid esters are extraordinarily easy to move, it was rather to be assumed that the reactants at least would partially react to form quaternary compounds.
Diese Reaktion konnte auch beobachtet werden, wenn phenylsubstituierte Diamine als Reaktionspartner verwendet werden.This reaction could also be observed when using phenyl-substituted diamines as reactants will.
709 509/433709 509/433
α-[ (/ϊ-Dimethylamino-äthyl) -methyl-amino] -α- [(/ ϊ-Dimethylamino-ethyl) -methyl-amino] -
phenylessigsäure-n-nonylesterphenylacetic acid n-nonyl ester
Ein Gemisch aus 100 g α-Chlor-phenyl-essigsäuren-nonylester und 60 g Trimethyläthylendiamm wird unter Rühren 4 Stunden am- Rückflußkühler auf 150° erhitzt. Das Reaktionsprodukt wird nach dem Erkalten in Wasser gelöst, mit Salzsäure angesäuert und zur Entfernung von unverändertem a - Chlor -phenyl - essigsäure - η - nonylester mit Äther ausgeschüttelt. Der wäßrige Anteil wird mit Natronlauge alkalisch gemacht, ausgeäthert und der Ätherauszug mit Natriumsulfat getrocknet. Nach Abdestillieren des Äthers wird der Rückstand im Vakuum destilliert.A mixture of 100 g of α-chloro-phenyl-acetic acid nonyl ester and 60 g of trimethylethylenediamine is heated to 150 ° for 4 hours in a reflux condenser with stirring. The reaction product is released after cooling in water, acidified with hydrochloric acid and for the removal of the natural a - chloro phenyl - acetic acid - η - nonyl extracted with ether. The aqueous portion is made alkaline with sodium hydroxide solution, extracted with ether and the ether extract is dried with sodium sulfate. After the ether has been distilled off, the residue is distilled in vacuo.
Kp.0>03 160 bis 165°.Kp. 0> 0 3 160 to 165 °.
In analoger Weise werden a-[(/?-Diäthylamino-isopropyl)-äthyl-amino]-phenyl-essigsäure-n-nonylester, Kp.0j05 178 bis 182°, und a-[(^-Dimethylamino-äthyl)-methylamino]-phenyl-essigsäure-isoamylester, Kp.OiC1 125 bis 130°, hergestellt.Kp -phenyl-acetic acid-n-nonyl, 0j05 178-182 °, and a in a manner analogous to a be - - [ethyl-amino (diethylamino-isopropyl /?)] -. [(^ - dimethylamino-ethyl) methylamino ] phenylacetic acid isoamyl ester, bp. OiC1 125 to 130 °.
-COO —R3 -COO -R 3
R1-N-CH-CH2-NR 1 -N-CH-CH 2 -N
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEA17418A DE1008308B (en) | 1953-02-09 | 1953-02-09 | Process for the preparation of ª[(ª-dialkylamino-alkyl)-alkyl-amino]-phenyl-acetic acid isoamyl and -n-nonyl esters |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEA17418A DE1008308B (en) | 1953-02-09 | 1953-02-09 | Process for the preparation of ª[(ª-dialkylamino-alkyl)-alkyl-amino]-phenyl-acetic acid isoamyl and -n-nonyl esters |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1008308B true DE1008308B (en) | 1957-05-16 |
Family
ID=6923883
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEA17418A Pending DE1008308B (en) | 1953-02-09 | 1953-02-09 | Process for the preparation of ª[(ª-dialkylamino-alkyl)-alkyl-amino]-phenyl-acetic acid isoamyl and -n-nonyl esters |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1008308B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0058373A1 (en) * | 1981-02-12 | 1982-08-25 | Ciba-Geigy Ag | Substituted aliphatic secondary amines and their salts, pharmaceutical compositions containing them and their use |
| US4723031A (en) * | 1984-08-27 | 1988-02-02 | Chevron Research Company | Processes for synthesizing substituted and unsubstituted aminoacetate esters |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE842206C (en) * | 1950-01-28 | 1952-06-23 | Asta Werke Ag Chem Fab | Process for the N-alkylation of ª ‡ -aminophenyl acetic acid esters |
-
1953
- 1953-02-09 DE DEA17418A patent/DE1008308B/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE842206C (en) * | 1950-01-28 | 1952-06-23 | Asta Werke Ag Chem Fab | Process for the N-alkylation of ª ‡ -aminophenyl acetic acid esters |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0058373A1 (en) * | 1981-02-12 | 1982-08-25 | Ciba-Geigy Ag | Substituted aliphatic secondary amines and their salts, pharmaceutical compositions containing them and their use |
| US4723031A (en) * | 1984-08-27 | 1988-02-02 | Chevron Research Company | Processes for synthesizing substituted and unsubstituted aminoacetate esters |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE1183508B (en) | Process for the preparation of N-allyl-14-hydroxydihydronormorphinone and its salts | |
| DE1008308B (en) | Process for the preparation of ª[(ª-dialkylamino-alkyl)-alkyl-amino]-phenyl-acetic acid isoamyl and -n-nonyl esters | |
| DE2000030C3 (en) | 3-alkoxy- and 3-phenoxy-2- (diphenylhydroxy) methyl-propylamines and medicaments containing them | |
| DE2351281B2 (en) | Aminophenylethanolamine derivatives, their production and use | |
| AT354644B (en) | METHOD FOR PRODUCING NEW SALTS OF ALKALOID DERIVATIVES FROM THIOPHOSPHORIC ACID | |
| DE2403786A1 (en) | NEW DERIVATIVES OF CUMARINE | |
| DE1670478A1 (en) | Process for the preparation of derivatives of alpha-piperazino-phenylacetonitrile | |
| AT273967B (en) | Process for the preparation of new salts of substituted s-triazines | |
| DE1007335B (en) | Process for the preparation of new chlorinated benzoic acid alcohol esters | |
| AT229290B (en) | Process for the preparation of 5- (3'-aminopropylidene) -dibenzo- [a, d] -cyclohepta- [1,4] -dienes and their acid addition salts | |
| AT265530B (en) | Process for the preparation of new isoquinoline derivatives | |
| AT251585B (en) | Process for the preparation of new 6,7-dihydro-5H-pyrrolo- [3,4-d] -pyrimidines | |
| AT338768B (en) | PROCESS FOR PREPARATION OF NEW PHENOXYALCANIC ACID AMIDES | |
| AT240365B (en) | Process for the preparation of new sulfonamide derivatives and their salts | |
| AT227256B (en) | Process for the production of new aminoindanes and their salts | |
| AT234691B (en) | Process for the preparation of new piperidine derivatives | |
| AT288400B (en) | Process for the preparation of new cinnamic acid amides | |
| AT260935B (en) | Process for the preparation of new 5,6-dihydro-5-oxo-11H-pyrido [2,3-b] [1,5] benzodiazepines | |
| AT293423B (en) | Process for the preparation of substituted acetylguanidines and their acid addition salts | |
| DE2403682C3 (en) | S-methyl-Z-phenyl-S-benzothiazole n-acylic acid compounds and process for their preparation | |
| DE825548C (en) | Process for the preparation of new diquartar salts of pyrimidylaminocinnolines | |
| CH390940A (en) | Process for the preparation of 1,4-benzdioxane derivatives | |
| AT248433B (en) | Process for the preparation of new ω-phenyl-ω-pyridyl-alkylamine derivatives | |
| DE1118204B (en) | Process for the preparation of basic theophyllinyl acetic acid esters | |
| DE1193499B (en) | Process for the production of new sulfonamides |