US2665300A - Method for the n-alkylation of phenylaminoacetic acid esters - Google Patents
Method for the n-alkylation of phenylaminoacetic acid esters Download PDFInfo
- Publication number
- US2665300A US2665300A US207446A US20744651A US2665300A US 2665300 A US2665300 A US 2665300A US 207446 A US207446 A US 207446A US 20744651 A US20744651 A US 20744651A US 2665300 A US2665300 A US 2665300A
- Authority
- US
- United States
- Prior art keywords
- alkylation
- acid esters
- hydrochloride
- phenylaminoacetic acid
- solvents
- 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 - Lifetime
Links
- NPKSPKHJBVJUKB-UHFFFAOYSA-N N-phenylglycine Chemical class OC(=O)CNC1=CC=CC=C1 NPKSPKHJBVJUKB-UHFFFAOYSA-N 0.000 title description 6
- 238000000034 method Methods 0.000 title description 4
- 238000005804 alkylation reaction Methods 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 8
- 229960003424 phenylacetic acid Drugs 0.000 claims description 4
- 239000003279 phenylacetic acid Substances 0.000 claims description 4
- 239000002904 solvent Substances 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 238000007126 N-alkylation reaction Methods 0.000 description 7
- 239000012458 free base Substances 0.000 description 6
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- -1 amino radicals Chemical class 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- OVJJILSKYWXGBM-UHFFFAOYSA-N phenamacide Chemical compound CC(C)CCOC(=O)C(N)C1=CC=CC=C1 OVJJILSKYWXGBM-UHFFFAOYSA-N 0.000 description 4
- 208000007101 Muscle Cramp Diseases 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- RAGSWDIQBBZLLL-UHFFFAOYSA-N 2-chloroethyl(diethyl)azanium;chloride Chemical compound Cl.CCN(CC)CCCl RAGSWDIQBBZLLL-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- MZVQCMJNVPIDEA-UHFFFAOYSA-N [CH2]CN(CC)CC Chemical group [CH2]CN(CC)CC MZVQCMJNVPIDEA-UHFFFAOYSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- LQLJZSJKRYTKTP-UHFFFAOYSA-N 2-dimethylaminoethyl chloride hydrochloride Chemical compound Cl.CN(C)CCCl LQLJZSJKRYTKTP-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Definitions
- the compound obtained by the N-alkylation of phenylaminoacetic acid iso-amyl ester is characterised in the form of its hydrochloride by excellent cramp-relieving action. It is in particular suitable for the treatment of spasms due to muscular or neural causes.
- hydrochloride of dialkylaminoethyl chloride unlike the free base, is quite stable, it can be stored without any trouble and can be using the free base where the base used must be prepared from the hydrochloride with a considerable loss, and the base on account of its sensitivity and instability must be specially prepared from the hydrochloride for each operation.
- hydrochloride of the isoamylester of alpha- (N' diethylaminoethyl N amino) phenylacetic acid As a novel therapeutically useful compound the hydrochloride of the isoamylester of alpha- (N' diethylaminoethyl N amino) phenylacetic acid.
- a method for producing the isoamylester of alpha (N' diethylaminoethyl N amino)- phenylacetic acid which comprises reacting alpha 4 phenylaminoacetic acid isoamyl ester in the absence of solvents with diethylaminoethyl-chloride hydrochloride.
- a method for producing the isoamylester of alpha (N dimethylaminoethyl N amino) phenylacetic acid which comprises reacting alpha phenylaminoacetic acid isoamylester in the absence of solvents with dimethylaminoethylchloride hydrochloride.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Patented Jan. 5, 1954 METHOD FOR THE N-ALKYLATI ON OF PHENYLAMINOACETIC ACID ESTERS Norbert Brock, .Brackvve Gadderbaum, and Mai- Germany, assignors 'ges'ellschaft, Chemise Westphalia, Germany as, sli htrt *Kiihiis, tin Schmeisser, Munich,
to Asta-Werke Aktienhe Fabrik, 'Brackw''de,
No Drawing. Application January 23, 1951, Serial No. 207,446
Claims priority, application Austria January 25, 1950 4 Claims.
It is well known that compounds having aromatically bonded amino groups can be converted into the corresponding N-alkyl compounds by the action of dialkylaminoalkylchlorides. This reaction is generally carried out using the dialkylaminoalkylchloride in the form of a free base in the presence of neutral solvents. There is no information regarding the yield produced by this reaction.
As far as we are aware N-alkylations of phenylaminoacetic acid esters have not been carried out. Attempts to obtain the N-alkylation of phenylamino-acetic acid esters by the abovementioned usual method, that is, by using the free base in the presence of neutral solvents have given very poor yields, in general not more than 20%.
On the other hand it has been discovered that surprisingly high yields of N-alkylation products are obtained in the N-alkylation of phenylaminoacetic acid esters, provided that the reaction is carried out in the absence of solvents with the aid of the hydrochloride of the dialkylami noalkylchloride base. Under these conditions yields of 80% or more are obtained. It has been found that particularly good results are obtained if phenylaminoacetic acid iso-amylester is reacted, for example, with diethylaminoethylchloride hydrochloride in the absence of solvents. In this manner on the one hand, particularly high yields (over 80%) are obtained, while on the other hand, compounds are obtained which exhibit extremely valuable therapeutical properties.
Examples ish translucent mass follows:
The reaction product is dissolved in water, made alkaline and then ether is added. After drying the etheric solution with sodium sulphate, the ether is removed and the residue is fractionally distilled in vacuo. After slight forerunnings, the ester distils over at B. P4 165 to 180. Yield 58 g.=80.11%.
The compound obtained by the N-alkylation of phenylaminoacetic acid iso-amyl ester is characterised in the form of its hydrochloride by excellent cramp-relieving action. It is in particular suitable for the treatment of spasms due to muscular or neural causes.
Since the hydrochloride of dialkylaminoethyl chloride, unlike the free base, is quite stable, it can be stored without any trouble and can be using the free base where the base used must be prepared from the hydrochloride with a considerable loss, and the base on account of its sensitivity and instability must be specially prepared from the hydrochloride for each operation.
Occasionally N-alkylations of compounds containing aromatically bonded amino radicals and not belonging to the series of the phenylaminoaceticacid esters have also been carried out by using, instead of the free dialkylaminochloride base, the corresponding hydrochloride and by treating without solvents. There is however no data at hand to show that better yields are obtained than by the usual process using the free base. Therefore no conclusions could be drawn that in the N-alkylation of phenylamino acetic which may be treated as acid esters using the hydrochloride in the absence of solvents, yields could be obtained which are a multiple of, for example, four times the yield which is obtained by using the free base in the presence of solvents. It could not be foreseen either, that compounds according to the invention would be obtained with high yields, for example 80% or more, having special therapeutic properties in particular cramp-relieving actions as for example those exhibited by the N alkylation products of phenylaminoacetic acid iso-amyl ester, in the form of their hydrochlorides.
We claim: 1. As a novel therapeutically useful compound,
the isoamylester of alpha- (N' diethylamino- 5 C2115 CiH5 wherein R stands for the isoamyl radical.
2. As a novel therapeutically useful compound the hydrochloride of the isoamylester of alpha- (N' diethylaminoethyl N amino) phenylacetic acid.
3. A method for producing the isoamylester of alpha (N' diethylaminoethyl N amino)- phenylacetic acid which comprises reacting alpha 4 phenylaminoacetic acid isoamyl ester in the absence of solvents with diethylaminoethyl-chloride hydrochloride.
4. A method for producing the isoamylester of alpha (N dimethylaminoethyl N amino) phenylacetic acid which comprises reacting alpha phenylaminoacetic acid isoamylester in the absence of solvents with dimethylaminoethylchloride hydrochloride.
NORBERT BROCK. ENGELBERT KiiHAs. MARTIN SCHMEISSER.
References Cited in the file of this patent UNITED STATES PATENTS Number 1 H Name Date 1,958,469 Christmann et a1. May 15, 1934 2,176,441 Ulrich et a1. Oct. 17, 1939 20 2,230,774 Bockmeuhl et a1. Feb. 4, 1941 2,293,034 Moore Aug. 18, 1942 2,470,094 Dickey et a1 May 17, 1949
Claims (1)
1. AS A NOVEL THERAPEUTICALLY USEFUL COMPOUND, THE ISOAMYLESTER OF ALPHA - (N''-DIETHYLAMINOETHYL-N-AMINO) -PHENYLACETIC ACID OF THE FORMULA
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AT2665300X | 1950-01-25 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US2665300A true US2665300A (en) | 1954-01-05 |
Family
ID=3690334
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US207446A Expired - Lifetime US2665300A (en) | 1950-01-25 | 1951-01-23 | Method for the n-alkylation of phenylaminoacetic acid esters |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US2665300A (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1958469A (en) * | 1929-09-27 | 1934-05-15 | American Cyanamid Co | Aliphatic acid antioxidants |
| US2176441A (en) * | 1935-04-04 | 1939-10-17 | Ig Farbenindustrie Ag | Removal of gaseous weak acid from gases containing the same |
| US2230774A (en) * | 1938-07-04 | 1941-02-04 | Winthrop Chem Co Inc | Basic esters and method of preparing them |
| US2293034A (en) * | 1941-05-22 | 1942-08-18 | American Cyanamid Co | Pest control composition |
| US2470094A (en) * | 1945-02-23 | 1949-05-17 | Eastman Kodak Co | Monoazo dye |
-
1951
- 1951-01-23 US US207446A patent/US2665300A/en not_active Expired - Lifetime
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1958469A (en) * | 1929-09-27 | 1934-05-15 | American Cyanamid Co | Aliphatic acid antioxidants |
| US2176441A (en) * | 1935-04-04 | 1939-10-17 | Ig Farbenindustrie Ag | Removal of gaseous weak acid from gases containing the same |
| US2230774A (en) * | 1938-07-04 | 1941-02-04 | Winthrop Chem Co Inc | Basic esters and method of preparing them |
| US2293034A (en) * | 1941-05-22 | 1942-08-18 | American Cyanamid Co | Pest control composition |
| US2470094A (en) * | 1945-02-23 | 1949-05-17 | Eastman Kodak Co | Monoazo dye |
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