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DE1119287B - Process for the preparation of blood pressure-effective secondary amines - Google Patents

Process for the preparation of blood pressure-effective secondary amines

Info

Publication number
DE1119287B
DE1119287B DEF28066A DEF0028066A DE1119287B DE 1119287 B DE1119287 B DE 1119287B DE F28066 A DEF28066 A DE F28066A DE F0028066 A DEF0028066 A DE F0028066A DE 1119287 B DE1119287 B DE 1119287B
Authority
DE
Germany
Prior art keywords
formula
carbon atoms
preparation
blood pressure
tert
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
Application number
DEF28066A
Other languages
German (de)
Inventor
Dr Rudolf Hiltmann
Dr Hartmund Wollweber
Dr Wolfgang Wirth
Dr Rudolf Goesswald
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bayer AG
Original Assignee
Bayer AG
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Bayer AG filed Critical Bayer AG
Priority to DEF28066A priority Critical patent/DE1119287B/en
Priority to BE589125A priority patent/BE589125A/en
Priority to FR837167A priority patent/FR456M/fr
Publication of DE1119287B publication Critical patent/DE1119287B/en
Pending legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C213/02Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C217/00Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
    • C07C217/02Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C217/04Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C217/06Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted
    • C07C217/08Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to an acyclic carbon atom

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Description

DEUTSCHESGERMAN

PATENTAMTPATENT OFFICE

F28066IVb/12qF28066IVb / 12q

ANMELDETAG: 28. MÄRZ 1959REGISTRATION DATE: MARCH 28, 1959

BEKANNTMACHUNG DER ANMELDUNG UNDAUSGABE DER AUSLEGESCHRIFT: 14. DEZEMBER 1961NOTICE THE REGISTRATION AND ISSUE OF EDITORIAL: DECEMBER 14, 1961

Es wurde gefunden, daß sekundäre Amine der allgemeinen FormelIt has been found that secondary amines of the general formula

CH,CH,

R —CH2-C —NH-R —CH 2 -C —NH-

CH3 CH 3

,R', R '

R"R "

sich durch ihre starke blutdrucksenkende und ganglienblockierende Wirkung auszeichnen. In der Formel bedeutet R Wasserstoff oder eine gerade oder verzweigte Alkylgruppe mit 1 bis 4 Kohlenstoffatomen, R' einen Alkylrest mit 1 bis 3 Kohlenstoffatomen und R" einen gesättigten oder ungesättigten Alkylrest mit 1 bis 3 Kohlenstoffatomen, der durch Hydroxylgruppen substituiert sein kann.are characterized by their strong antihypertensive and ganglion-blocking effect. In the formula means R is hydrogen or a straight or branched alkyl group with 1 to 4 carbon atoms, R 'is one Alkyl radical with 1 to 3 carbon atoms and R ″ a saturated or unsaturated alkyl radical with 1 to 3 Carbon atoms, which can be substituted by hydroxyl groups.

Für die Herstellung der erfindungsgemäß erhältlichen Amine kann man z. B. reaktionsfähige Halogenwasserstoffsäure-, Alkyl- oder Arylsulfonsäureester von Alkoholen der FormelFor the preparation of the amines obtainable according to the invention you can, for. B. reactive hydrohalic acid, Alkyl or aryl sulfonic acid esters of alcohols of the formula

ho—ch:high:

-R'-R '

1R" 1 R "

mit primären Aminen der Formelwith primary amines of the formula

R — CH2 — C(CH3)2 — NH2 R - CH 2 - C (CH 3 ) 2 - NH 2

in an sich bekannter Weise umsetzen.
Ferner kann man an Schiffsche Basen der Formel
implement in a manner known per se.
Furthermore, one can use Schiff's bases of the formula

R — CH2 — C(CHs)2 -N = CH-R'
R — CH2 — C(CH3)2 — N = CH — R"
R - CH 2 - C (CHs) 2 -N = CH-R '
R - CH 2 - C (CH 3 ) 2 - N = CH - R "

Grignardverbindungen anlagern und die Produkte anschließend hydrolysieren.Add Grignard compounds and then hydrolyze the products.

Die erfindungsgemäß erhaltenen sekundären tert.-Alkylamine sind farblose Flüssigkeiten, die sich im Vakuum ohne Zersetzung destillieren lassen und die in organischen Lösungsmitteln löslich sind. Sie bilden mit anorganischen oder organischen Säuren gut kristallisierte, beständige Salze, die sich in Wasser lösen.The secondary tert-alkylamines obtained according to the invention are colorless liquids which are in the Allow vacuum to distill without decomposition and which are soluble in organic solvents. they form stable salts, well crystallized with inorganic or organic acids, which dissolve in water to solve.

Beispiel 1example 1

73 g tert.-Butylamin werden mit 172 g Isopropyljodid im Autoklav zuerst 6 Stunden auf 150° C und dann 6 Stunden auf 2000C erhitzt. Man löst den festgewordenen Autoklaveninhalt in 250 ml Wasser, filtriert ab, setzt die Base aus der wäßrigen Lösung mit konzentrierter Natronlauge in Freiheit und äthert aus. Nach Fraktionierung der ätherischen Lösung Verfahren zur Herstellung
blutdruckwirksamer sekundärer Amine
73 g of tert-butylamine are heated to 200 0 C and 172 g of isopropyl iodide in the first autoclave 6 hours at 150 ° C and then 6 hours. The solidified contents of the autoclave are dissolved in 250 ml of water, filtered off, the base is released from the aqueous solution with concentrated sodium hydroxide solution and left with ether. After fractionation of the essential solution method of preparation
blood pressure acting secondary amines

Anmelder:Applicant:

Farbenfabriken Bayer Aktiengesellschaft,
Leverkusen-Bayerwerk
Paint factories Bayer Aktiengesellschaft,
Leverkusen-Bayerwerk

Dr. Rudolf Hiltmann, Dr. Hartmund Wollweber,Dr. Rudolf Hiltmann, Dr. Hartmund Wollweber,

Dr. Wolfgang Wirth, Wuppertal-Elberfeld,
und Dr. Rudolf Gösswald, Wuppertal-Vohwinkel,
sind als Erfinder genannt worden
Dr. Wolfgang Wirth, Wuppertal-Elberfeld,
and Dr. Rudolf Gösswald, Wuppertal-Vohwinkel,
have been named as inventors

erhält man 53 g tert.-Butylisopropylamin vom Kp.76O 98 bis 990C.is obtained 53 g of tert-butylisopropylamine from Kp. 76o 98 to 99 0 C.

Zur Überführung in das Hydrochlorid löst man dasTo convert it into the hydrochloride, this is dissolved

tert-Butylisopropylamin in Äther, versetzt mit der berechneten Menge ätherischer Salzsäure, filtriert ab und kristallisiert aus Methyläthylketon um. F. 196 bis 197° C.tert-Butylisopropylamine in ether, mixed with the calculated amount of ethereal hydrochloric acid, filtered off and recrystallized from methyl ethyl ketone. F. 196 up to 197 ° C.

Beispiel 2Example 2

73 g tert.-Butylamin und 130 g p-Toluolsulfosäure-3-pentylester werden 24 Stunden im Autoklav auf 100° C erhitzt. Nach Erkalten löst man den Inhalt des Autoklavs in wenig Wasser, macht mit Natronlauge stark alkalisch und treibt das Basengemisch mit Wasserdampf über. Aus dem Destillat trennt man das Öl ab, trocknet mit festem Kaliumhydroxyd und destilliert an einer 50-cm-Kolonne. Nach einem Vorlauf von tert-Butylamin erhält man 23,1 g N-tert.-Butyl-3-pentylamin vom Kp. 145°C; Hydrochlorid Schmp. 229,5 bis 230° C.73 g of tert-butylamine and 130 g of p-toluenesulfonic acid 3-pentyl ester are heated to 100 ° C in an autoclave for 24 hours. After cooling down, the content of the Autoclave in a little water, makes strongly alkaline with sodium hydroxide solution and drives the base mixture with it Water vapor over. The oil is separated off from the distillate, dried with solid potassium hydroxide and distilled on a 50 cm column. After a first run of tert-butylamine, 23.1 g of N-tert-butyl-3-pentylamine are obtained of bp 145 ° C; Hydrochloride m.p. 229.5 to 230 ° C.

Der durch Umsetzen von Pentan-3-ol mit p-Toluolsulfonylchlorid in Pyridin erhältliche p-Toluolsulfosäure-3-pentylester ist kristallisiert und wird ohne weitere Reinigung eingesetzt.That by reacting pentan-3-ol with p-toluenesulfonyl chloride 3-pentyl p-toluenesulfonate obtainable in pyridine has crystallized and is used without further purification.

Nach dem gleichen Arbeitsverfahren werden aus 60 g p-Toluolsulfonsäure-2-butylester und 50 g tert.-Butylamin 7 g N-tert.-Butyl-2-butylamin (Kp.75O 115 bis 117°C; Hydrochlorid F. 173 bis 174°C) gewonnen.Using the same procedure, 60 g of 2-butyl p-toluenesulfonate and 50 g of tert-butylamine are converted into 7 g of N-tert-butyl-2-butylamine ( b.p. 75O 115 to 117 ° C; hydrochloride mp 173 to 174 ° C).

Beispiel 3Example 3

73 g tert.-Butylamin und 140 g p-Toluolsulfosäure-2-(4-methylpentyl)-ester, der aus 4-Methylpentan-2-ol73 g tert-butylamine and 140 g p-toluenesulfonic acid 2- (4-methylpentyl) ester, that from 4-methylpentan-2-ol

109 749/540109 749/540

und p-Toluolsulfonylchlorid in Pyridin als Öl erhalten wird, erhitzt man 24 Stunden auf 1000C und arbeitet nach der im Beispiel 2 angegebenen Arbeitsweise auf. N-tert.-Butyl-2-(4-methylpentyl)-amin destilliert bei 160 bis 161,5°C. Ausbeute 29,2 g; Hydrochlorid Schmp. 136 bis 1370C.and p-toluenesulfonyl chloride in pyridine is obtained as an oil, it is heated to 100 ° C. for 24 hours and worked up according to the procedure given in Example 2. N-tert-butyl-2- (4-methylpentyl) amine distilled at 160 to 161.5 ° C. Yield 29.2 g; Hydrochloride mp. 136-137 0 C.

Beispiel 4Example 4

53 g tert.-Amylamin werden mit 63 g Isopropylbromid und 50 ecm Glycerin 30 Stunden unter Rückfluß erhitzt. Man destilliert das Reaktionsprodukt an der Widmerkolonne und erhält 30 g N-tert.-Amyl-2-propylamin, Κρ.7β0 125 bis 127°C; Hydrochlorid F. 138°C.53 g of tert-amylamine are refluxed for 30 hours with 63 g of isopropyl bromide and 50 ecm of glycerol. The reaction product is distilled on the Widmer column and 30 g of N-tert-amyl-2-propylamine, Κρ, are obtained. 7β0 125 to 127 ° C; Hydrochloride mp 138 ° C.

In der gleichen Arbeitsweise erhält man aus tert.-Butylamin und sek.-Amylbromid N-tert.-Butylamino-2-pentan, Kp.7B0 138 bis 1400C; Hydrochlorid F. 185 bis 186° C.In the same operation is obtained from tert-butyl and sec-amyl bromide N-tert-butylamino-2-pentane, bp 7B0 138 to 140 0 C. Hydrochloride F. 185 to 186 ° C.

Claims (1)

PATENTANSPRUCH: ao PATENT CLAIM: ao Verfahren zur Herstellung blutdruckwirksamer sekundärer Amine der allgemeinen FormelProcess for the preparation of blood pressure-effective secondary amines of the general formula CH3 CH 3 r_ch2—c—nh—ch;r_ch 2 -c-nh-ch; ,R', R ' CH3
wobei R Wasserstoff oder eine gerade oder verzweigte Alkylgruppe mit 1 bis 4 Kohlenstoffatomen und R' einen Alkylrest mit 1 bis 3 Kohlenstoffatomen und R" einen gesättigten oder ungesättigten Alkylrest mit 1 bis 3 Kohlenstoffatomen, der durch Hydroxylgruppen substituiert sein kann, bedeutet, dadurch gekennzeichnet, daß man entweder
CH 3
where R denotes hydrogen or a straight or branched alkyl group with 1 to 4 carbon atoms and R 'denotes an alkyl group with 1 to 3 carbon atoms and R "denotes a saturated or unsaturated alkyl group with 1 to 3 carbon atoms which can be substituted by hydroxyl groups, characterized in that that one either
a) reaktionsfähige Halogenwasserstoffsäure-, Alkyl- oder Arylsulfonsäureester von Alkoholen der Formela) reactive hydrohalic acid, alkyl or aryl sulfonic acid esters of alcohols the formula ,R', R ' ho—ch;high; mit primären Aminen der Formel
R — CH2 — C(CH3)2 — NH2
umsetzt oder daß man
with primary amines of the formula
R - CH 2 - C (CH 3 ) 2 - NH 2
implement or that one
b) an Schiffsche Basen der Formelb) on Schiff bases of the formula R — CH2 — C(CHs)2 — N = CH — R'
bzw.
R — CH2 — C(CH3)2 — N = CH — R"
R - CH 2 - C (CHs) 2 - N = CH - R '
respectively.
R - CH 2 - C (CH 3 ) 2 - N = CH - R "
Grignardverbindungen addiert und die Produkte anschließend zu den sekundären Aminen hydrolysiertGrignard compounds are added and the products are then added to the secondary ones Amines hydrolyzed und die so erhaltenen Basen gegebenenfalls in Salze überführt.and the bases obtained in this way are optionally converted into salts. ©109 749/540 12.61© 109 749/540 12.61
DEF28066A 1959-03-28 1959-03-28 Process for the preparation of blood pressure-effective secondary amines Pending DE1119287B (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
DEF28066A DE1119287B (en) 1959-03-28 1959-03-28 Process for the preparation of blood pressure-effective secondary amines
BE589125A BE589125A (en) 1959-03-28 1960-03-28 Manufacture of secondary amines acting on blood pressure.
FR837167A FR456M (en) 1959-03-28 1960-08-30

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DEF28066A DE1119287B (en) 1959-03-28 1959-03-28 Process for the preparation of blood pressure-effective secondary amines

Publications (1)

Publication Number Publication Date
DE1119287B true DE1119287B (en) 1961-12-14

Family

ID=7092731

Family Applications (1)

Application Number Title Priority Date Filing Date
DEF28066A Pending DE1119287B (en) 1959-03-28 1959-03-28 Process for the preparation of blood pressure-effective secondary amines

Country Status (3)

Country Link
BE (1) BE589125A (en)
DE (1) DE1119287B (en)
FR (1) FR456M (en)

Also Published As

Publication number Publication date
BE589125A (en) 1960-07-18
FR456M (en) 1961-04-24

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