DE2337931A1 - 2-Amino-N-cyclohexyl-3,5-dibromo-N-methylbenzyl-amine prepn - by reacting benzylalcohol with N,N',N''-tricyclohexyl-N,N',N''-trimethyl-phosphoric acid triamide - Google Patents
2-Amino-N-cyclohexyl-3,5-dibromo-N-methylbenzyl-amine prepn - by reacting benzylalcohol with N,N',N''-tricyclohexyl-N,N',N''-trimethyl-phosphoric acid triamideInfo
- Publication number
- DE2337931A1 DE2337931A1 DE19732337931 DE2337931A DE2337931A1 DE 2337931 A1 DE2337931 A1 DE 2337931A1 DE 19732337931 DE19732337931 DE 19732337931 DE 2337931 A DE2337931 A DE 2337931A DE 2337931 A1 DE2337931 A1 DE 2337931A1
- Authority
- DE
- Germany
- Prior art keywords
- amino
- dibromo
- tricyclohexyl
- trimethyl
- phosphoric acid
- 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
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 System
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/22—Amides of acids of phosphorus
- C07F9/224—Phosphorus triamides
Abstract
Description
Case 5/596
Dr.Pl./Kp.Case 5/596
Dr.Pl./Kp.
DR. KARL THOMAE-GMBH., BIBERACH AN DER RISSDR. KARL THOMAE-GMBH., BIBERACH AN DER RISS
Neues Verfahren zur Herstellung von 2-Amino-N-cyclohexyl-3,5-dibrom-N-methyl-benzylamin New process for the preparation of 2-amino-N-cyclohexyl- 3,5-dibromo-N-methyl-benzylamine
Es ist bekannt, daß 2-Amino-N-cyclohexyl-3»5-dibrom-N-methylbenzylamin der Formel I,It is known that 2-amino-N-cyclohexyl-3 »5-dibromo-N-methylbenzylamine of formula I,
und seine physiologisch verträglichen Säureadditionssalze mit anorganischen oder organischen Säuren wertvolle pharmakologische Eigenschaften aufweisen, insbesondere eine gute sekretolytische Wirkung.and its physiologically acceptable acid addition salts with inorganic ones or organic acids have valuable pharmacological properties, especially good secretolytic properties Effect.
überraschenderweise wurde nun gefunden, daß die obengenannte bindung der allgemeinen Formel I sich auch nach folgendem Verfahren herstellen läßt:Surprisingly, it has now been found that the above Binding of the general formula I can also be produced by the following process:
Umsetzung des Benzylalkohol der Formel II,Implementation of the benzyl alcohol of the formula II,
BrBr
09807/116909807/1169
mit der neuen Verbindung der Formel III,with the new compound of formula III,
(III)(III)
Die Umsetzung wird gegebenenfalls in einem inerten Lösungsmittel wie Tetralin bei erhöhten Temperaturen, z.B. bei Temperaturen zwischen 200 und 280 C, durchgeführt. Die Umsetzung kann jedoch auch ohne Lösungsmittel oder mit dem Amid der Formel III als Lösungsmittel durchgeführt werden.The reaction is optionally carried out in an inert solvent such as tetralin at elevated temperatures, e.g. at temperatures between 200 and 280 C. However, the implementation can can also be carried out without a solvent or with the amide of the formula III as a solvent.
Die erhaltene Verbindung der Formel I kann nach ihrer Isolierung, gewünschtenfalls in ihre physiologisch verträglichen Salze mit anorganischen oder organischen Säuren übergeführt werden. Als Säuren haben sich hierbei Salzsäure, Bromwasserstoffsäure, Schwefelsäure, Phosphorsäure, Milchsäure, Zitronensäure oder Maleinsäure als geeignet erwiesen.After isolation, the compound of formula I obtained can, if desired, be converted into its physiologically acceptable salts with inorganic salts or organic acids are converted. The acids here are hydrochloric acid, hydrobromic acid, sulfuric acid, Phosphoric acid, lactic acid, citric acid or maleic acid proved to be suitable.
Den als Ausgangsstoff verwendeten Benzylalkohol der Formel II erhält man beispielsweise durch Reduktion des 2-Amino-3,5-dibrombenzaldehyds. Die neue Ausgangsverbindung der Formel III läßt sich durch Umsetzung eines Phosphoroxyhalogenids mit dem N-Methyl-N-cyclohexylamin in Gegenwart einer tertiären organischen Base herstellen. The benzyl alcohol of the formula II used as starting material is obtained for example by reducing the 2-amino-3,5-dibromobenzaldehyde. The new starting compound of the formula III can be obtained by reacting a phosphorus oxyhalide with N-methyl-N-cyclohexylamine prepare in the presence of a tertiary organic base.
Das erfindungsgemäße Verfahren erbringt in glatter Reaktion und guten Ausbeuten das Benzylamin der Formel I. Dies ist insofern überraschend, als der Benzylalkohol der Formel II sich bei den reaktionsgemäßen Temperaturen bereits zersetzt und sein verändertes Verhalten in Gegenwart der neuen Verbindung III für den Fachmann nicht absehbar war.The process according to the invention produces the benzylamine of the formula I in smooth reaction and good yields. This is so Surprisingly, than the benzyl alcohol of the formula II in the reactive Temperatures already decomposed and its changed behavior in the presence of the new compound III for the person skilled in the art was not foreseeable.
509807/1169509807/1169
Die Verbindung III läßt sich ihrerseits in einfacher Reaktion herstellen und trägt damit wesentlich zu der guten Durchführbarkeit des erfindungsgemäßen Verfahrens bei.Compound III, for its part, can be prepared in a simple reaction and thus contributes significantly to the ease with which the method according to the invention can be carried out.
Im folgenden wird das erfindungsgemäße Verfahren durch Beispiele näher erläutert:The method according to the invention is explained in more detail below by means of examples:
306 g N-Methyl-cyclohexylamin werden unter Rühren während 20 Minuten
mit hS g Phosphoroxychlorid versetzt und dann 3 Stunden
unter Rückfluß gekocht (ölbad, 1700C). Anschließend wird die abgekühlte
Reaktionslösung in 1,2 1 Chloroform und 0,8 1 Wasser aufgenommen, die organische Phase noch zweimal mit Wasser, zweimal
mit 2n Essigsäure und einmal mit 2n Ammoniak ausgeschüttelt, mit Natriumsulfat getrocknet und eingeengt. Der Rückstand wird über
eine Kieselgelsäule mit Chloroform-Essigester (1:1) chromatographiert. Die entsprechenden Fraktionen werden vereinigt, eingeengt
und der Rückstand in Petroläther aufgenommen, wonach eine geringe Menge eines Nebenprodukts kristallisiert, das nach längerem
Stehen abgesaugt wird. Das Filtrat engt man zur Trockene ein, am Schluß bei 1000C und 15 Torr. Das als öl erhaltene N,Nf,N"-Tricyclohexyl-N,N',N"-trimethyl-phosphorsäuretriamid
kristallisiert langsam durch.
Schmelzpunkt: 60 - 61I0C.306 g N-methyl-cyclohexylamine are added, with stirring for 20 minutes with hS g of phosphorus oxychloride and then boiled for 3 hours under reflux (oil bath, 170 0 C). The cooled reaction solution is then taken up in 1.2 l of chloroform and 0.8 l of water, the organic phase is extracted twice more with water, twice with 2N acetic acid and once with 2N ammonia, dried with sodium sulfate and concentrated. The residue is chromatographed on a silica gel column with chloroform-ethyl acetate (1: 1). The appropriate fractions are combined and concentrated, and the residue is taken up in petroleum ether, after which a small amount of a by-product crystallizes, which is filtered off with suction after standing for a long time. The filtrate is concentrated to dryness, at the end at 100 ° C. and 15 torr. The N, N f , N "-tricyclohexyl-N, N ', N" -trimethyl-phosphoric acid triamide obtained as an oil slowly crystallizes through.
Melting point: 60 - 6 1 I 0 C.
Beispiel 1 2-Amino-N-cyclohexyl-3^5-dibrom-N-methyl-benzylaminexample 1 2-Amino-N-cyclohexyl-3 ^ 5-dibromo-N-methyl-benzylamine
0,56 g (0,002 Mol) 2-Amino-3,5-dibrom-benzylalkohol und 3,1 g (0,008 Mol) N,N',N"-Tricyclohexyl-N,N',N"-trimethyl-phosphorsäuretriamid werden 1 Stunde auf 23O°C erhitzt. Nach dem Abkühlen wird in Äther und 2n Ammoniak aufgenommen, die organische Phase0.56 g (0.002 mol) of 2-amino-3,5-dibromobenzyl alcohol and 3.1 g (0.008 mol) of N, N ', N "-tricyclohexyl-N, N', N" -trimethyl-phosphoric acid triamide are heated to 230 ° C. for 1 hour. After cooling, the organic phase is taken up in ether and 2N ammonia
509807/1169509807/1169
mit Wasser gewaschen, mit Natriumsulfat getrocknet und mit etwas absolutem Äthanol versetzt. Nach Zugabe von äthanolischer Salzsäure
kristallisiert das 2-Amino-N-cyclohexyl-3,5 benzylamin als Hydrochlorid aus.
Ausbeute: 0,46 g (55,8 % der Theorie);
Schmelzpunkt des Hydrochlorids; 232 - 235°C (Zers.)washed with water, dried with sodium sulfate and mixed with a little absolute ethanol. After the addition of ethanolic hydrochloric acid, the 2-amino-N-cyclohexyl-3,5 benzylamine crystallizes out as the hydrochloride.
Yield: 0.46 g (55.8 % of theory);
The melting point of the hydrochloride; 232 - 235 ° C (dec.)
509807/1169509807/1169
Claims (3)
Priority Applications (20)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19732337931 DE2337931A1 (en) | 1973-07-26 | 1973-07-26 | 2-Amino-N-cyclohexyl-3,5-dibromo-N-methylbenzyl-amine prepn - by reacting benzylalcohol with N,N',N''-tricyclohexyl-N,N',N''-trimethyl-phosphoric acid triamide |
FI1776/74A FI177674A (en) | 1973-07-26 | 1974-06-11 | |
AT510674A AT330739B (en) | 1973-07-26 | 1974-06-20 | PROCESS FOR THE PREPARATION OF 2-AMINO -N- CYCLOHEXYL -3,5- DIBROME -N- METHYL-BENZYLAMINE AND ITS ACID-ADDITION SALTS |
CS7500001285A CS184839B2 (en) | 1973-07-26 | 1974-06-25 | Method for producing triamide of n,n',n''-tricyclohexyl-n,n',n''-trimethyl phosphoric acid |
CS4467A CS170115B2 (en) | 1973-07-26 | 1974-06-25 | |
BG7400031992A BG24231A3 (en) | 1973-07-26 | 1974-06-28 | Method of preparing triamide of n,n,n-tricyclohexyl-n,n,n-trimethylphosphoric acid |
ES427954A ES427954A1 (en) | 1973-07-26 | 1974-07-04 | Preparation of n * n*n** tricyclohexylln * n*n**trimethyll triamidephosphate |
NL7409046A NL7409046A (en) | 1973-07-26 | 1974-07-04 | PROCESS FOR PREPARING 2-AMINO-N-CYCLO-HEXYL-3,5-DIBROOM-N-METHYLBENZYLAMINE. |
DK397274A DK135837C (en) | 1973-07-26 | 1974-07-23 | METHOD FOR THE PREPARATION OF N-CYCLOHEXYL-N-METHYL- (2-AMINO-3,5-DIBROMBENZYL) AMIN |
CH1023574A CH597147A5 (en) | 1973-07-26 | 1974-07-24 | |
HUTO1000A HU168460B (en) | 1973-07-26 | 1974-07-24 | |
HUTO972A HU167868B (en) | 1973-07-26 | 1974-07-24 | |
JP8559074A JPS5515465B2 (en) | 1973-07-26 | 1974-07-25 | |
CA205,645A CA1041120A (en) | 1973-07-26 | 1974-07-25 | Process for the preparation of 2-amino-n-cyclohexyl-3,5-dibromo-n-methyl-benzylamine |
PL1974173005A PL94273B1 (en) | 1973-07-26 | 1974-07-25 | |
SE7409685A SE7409685L (en) | 1973-07-26 | 1974-07-25 | |
AT535575A AT332427B (en) | 1973-07-26 | 1975-07-11 | PROCESS FOR PRODUCING THE NEW N, N ', N "- TRICYCLOHEXYL -N, N', N" - TRIMETHYL -PHOSPHORIC ACID TRIAMIDE |
DK468976A DK140409C (en) | 1973-07-26 | 1976-10-18 | PHOSPHORIC ACETRIAMIDE USED AS INTERMEDIATE IN THE PREPARATION OF N-CYCLOHEXYL-N-METHYL- (2-AMINO-3,5-DIBROMOBENZYL) AMINE |
SE7709869A SE7709869L (en) | 1973-07-26 | 1977-09-01 | N, N'N "-TRICYCLOHEXYL-N, N'N" -TRIMETHYL-PHOSPHORIC ACTRIAMID |
JP664878A JPS53101344A (en) | 1973-07-26 | 1978-01-24 | Preparation of n * n*n** tricyclohexylln * n*n**trimethyll triamidephosphate |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19732337931 DE2337931A1 (en) | 1973-07-26 | 1973-07-26 | 2-Amino-N-cyclohexyl-3,5-dibromo-N-methylbenzyl-amine prepn - by reacting benzylalcohol with N,N',N''-tricyclohexyl-N,N',N''-trimethyl-phosphoric acid triamide |
Publications (1)
Publication Number | Publication Date |
---|---|
DE2337931A1 true DE2337931A1 (en) | 1975-02-13 |
Family
ID=5888014
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE19732337931 Pending DE2337931A1 (en) | 1973-07-26 | 1973-07-26 | 2-Amino-N-cyclohexyl-3,5-dibromo-N-methylbenzyl-amine prepn - by reacting benzylalcohol with N,N',N''-tricyclohexyl-N,N',N''-trimethyl-phosphoric acid triamide |
Country Status (14)
Country | Link |
---|---|
JP (2) | JPS5515465B2 (en) |
AT (1) | AT330739B (en) |
BG (1) | BG24231A3 (en) |
CA (1) | CA1041120A (en) |
CH (1) | CH597147A5 (en) |
CS (2) | CS170115B2 (en) |
DE (1) | DE2337931A1 (en) |
DK (1) | DK135837C (en) |
ES (1) | ES427954A1 (en) |
FI (1) | FI177674A (en) |
HU (2) | HU168460B (en) |
NL (1) | NL7409046A (en) |
PL (1) | PL94273B1 (en) |
SE (2) | SE7409685L (en) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3107760A1 (en) * | 1981-02-28 | 1982-09-23 | Gebr. Happich Gmbh, 5600 Wuppertal | UPHOLSTERY BODY FOR THE INTERIOR OF VEHICLES, IN PARTICULAR ARMREST |
JPH061882Y2 (en) * | 1988-11-16 | 1994-01-19 | 株式会社東海理化電機製作所 | Mirror body holding structure for vehicle outside mirror |
-
1973
- 1973-07-26 DE DE19732337931 patent/DE2337931A1/en active Pending
-
1974
- 1974-06-11 FI FI1776/74A patent/FI177674A/fi unknown
- 1974-06-20 AT AT510674A patent/AT330739B/en not_active IP Right Cessation
- 1974-06-25 CS CS4467A patent/CS170115B2/cs unknown
- 1974-06-25 CS CS7500001285A patent/CS184839B2/en unknown
- 1974-06-28 BG BG7400031992A patent/BG24231A3/en unknown
- 1974-07-04 ES ES427954A patent/ES427954A1/en not_active Expired
- 1974-07-04 NL NL7409046A patent/NL7409046A/en not_active Application Discontinuation
- 1974-07-23 DK DK397274A patent/DK135837C/en active
- 1974-07-24 CH CH1023574A patent/CH597147A5/xx not_active IP Right Cessation
- 1974-07-24 HU HUTO1000A patent/HU168460B/hu unknown
- 1974-07-24 HU HUTO972A patent/HU167868B/hu unknown
- 1974-07-25 PL PL1974173005A patent/PL94273B1/pl unknown
- 1974-07-25 JP JP8559074A patent/JPS5515465B2/ja not_active Expired
- 1974-07-25 CA CA205,645A patent/CA1041120A/en not_active Expired
- 1974-07-25 SE SE7409685A patent/SE7409685L/xx unknown
-
1977
- 1977-09-01 SE SE7709869A patent/SE7709869L/en unknown
-
1978
- 1978-01-24 JP JP664878A patent/JPS53101344A/en active Pending
Also Published As
Publication number | Publication date |
---|---|
ATA510674A (en) | 1975-10-15 |
CH597147A5 (en) | 1978-03-31 |
FI177674A (en) | 1975-01-27 |
DK397274A (en) | 1975-04-01 |
ES427954A1 (en) | 1976-09-01 |
HU167868B (en) | 1975-12-25 |
PL94273B1 (en) | 1977-07-30 |
JPS5515465B2 (en) | 1980-04-23 |
DK135837C (en) | 1977-12-05 |
CS170115B2 (en) | 1976-08-27 |
DK135837B (en) | 1977-07-04 |
JPS5047945A (en) | 1975-04-28 |
SE7709869L (en) | 1977-09-01 |
AT330739B (en) | 1976-07-12 |
BG24231A3 (en) | 1978-01-10 |
CA1041120A (en) | 1978-10-24 |
HU168460B (en) | 1976-04-28 |
SE7409685L (en) | 1975-01-27 |
CS184839B2 (en) | 1978-09-15 |
JPS53101344A (en) | 1978-09-04 |
NL7409046A (en) | 1975-01-28 |
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Legal Events
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