NO118258B

NO118258B -

Info

Publication number: NO118258B
Application number: NO15908465A
Authority: NO
Inventors: Igl E Hofmann
Original assignee: Lemm & Co Gmbh Ind Werke
Priority date: 1964-08-06
Filing date: 1965-07-24
Publication date: 1969-12-01
Also published as: BE666231A; NL6507529A; GB1107417A; DE1906928U; FR1442165A

Description

Fremgangsmåte til fremstilling av terapeutisk virksomme aminer. Process for the production of therapeutically active amines.

Foreliggende oppfinnelse angår en The present invention relates to a

fremgangsmåte for fremstilling av tera- method for the production of tera-

peutisk virksomme aminer med den generelle formel therapeutically active amines of the general formula

i hvilken n betyr tallet 0 eller 1, in which n means the number 0 or 1,

R Vannstoff eller en alkyl- eller acyl-gruppe og R Hydrogen or an alkyl or acyl group and

R, en tertiær aminogruppe, R, a tertiary amino group,

og for salter av disse aminer. and for salts of these amines.

I forannevnte formel henviser uttryk-ket «alkylen» til toverdige, alifatiske kull-vannstof f radikaler med rettlinjet eller for-grenet kjede. De ved bokstaven R angitte alkylradikaler er fortrinsvis lavere alkyl-grupper, som metyl, etyl, propyl og lignende. Den med bokstaven R betegnede acylrest kan være f. eks. acetyl-, propionyl-, ben-zoyl- eller difenylacetylresten etc. De med bokstaven Ri betegnede tertiære amino-grupper omfatter dialkylaminorester, som f. eks. dimetylaminoresten og mettede ba-siske monocykliske, fem- eller seks-leddete heterocykliske radikaler, som f. eks. piperidin-, morfolin- eller pyrrolidinradikalet. Oppfinnelsen omfatter også fremstillingen av saltene av aminene etter ovenstående generelle formel. Slike salter er f. eks. de med anorganiske syrer, f. eks. klorvann-stoffsyre, bromvannstoffsyre, jodvannstoff-syre, svovelsyre, fosforsyre etc, med orga-niske syrer, som f. eks. oksalsyre, citron-syre, eddiksyre, melkesyre, vinsyre, benzol-sulfonsyre og lignende, og med kvaternise-rende midler, f. eks. med alkylhalogenider, In the aforementioned formula, the term "alkylene" refers to divalent, aliphatic carbon-hydrogen f radicals with a straight or branched chain. The alkyl radicals indicated by the letter R are preferably lower alkyl groups, such as methyl, ethyl, propyl and the like. The acyl residue denoted by the letter R can be e.g. the acetyl, propionyl, benzoyl or diphenylacetyl residue etc. The tertiary amino groups denoted by the letter Ri comprise dialkylamino residues, such as e.g. the dimethylamino residue and saturated basic monocyclic, five- or six-membered heterocyclic radicals, such as e.g. the piperidine, morpholine or pyrrolidine radical. The invention also encompasses the preparation of the salts of the amines according to the above general formula. Such salts are e.g. those with inorganic acids, e.g. Hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, phosphoric acid, etc., with organic acids, such as e.g. oxalic acid, citric acid, acetic acid, lactic acid, tartaric acid, benzene sulphonic acid and the like, and with quaternizing agents, e.g. with alkyl halides,

som etylbromid, etyljodid, n-butylklorid, med dialkylsulfater, f. eks. dimetylsulfat, og such as ethyl bromide, ethyl iodide, n-butyl chloride, with dialkyl sulphates, e.g. dimethyl sulfate, and

med aralkylhalogenider, f. eks. benzoyl-bromid og lignende. Produktene etter fremgangsmåten ifølge oppfinnelsen har en be-merkelsesverdig virkning mot protozoer, f. with aralkyl halides, e.g. benzoyl bromide and the like. The products according to the method according to the invention have a remarkable effect against protozoa, e.g.

eks. Trichomonas vaginalis, og mot pato-gene sopper, f. eks. Tricophyton menta-grophytes og Microsporon lanosum. Videre kan særlig de bis-kvaternære ammonium-salter anvendes som Anthelmintica, f. eks. ved behandling av infeksjoner i Syphacia e.g. Trichomonas vaginalis, and against pathogenic fungi, e.g. Tricophyton menta-grophytes and Microsporon lanosum. Furthermore, the bis-quaternary ammonium salts in particular can be used as Anthelmintics, e.g. in the treatment of infections in Syphacia

obvelata. De bis-kvaternære ammonium-salter har dessuten en dempende virkning obvelata The bis-quaternary ammonium salts also have a dampening effect

på irritasjonsoverføring gjennom gangliene og kan derfor anvendes som ganglieblok-kerende middel. on irritation transmission through the ganglia and can therefore be used as a ganglia-blocking agent.

Fremgangsmåten etter oppfinnelsen for fremstilling av nevnte terapeutisk virksomme aminer etter ovenstående generelle formel henholdsvis disses salter karakteri-seres ved at man omsetter (3-jonon eller 4-[2,6,6-trimetyl-cykloheksen- (1) -yl] -2-metyl-buten(2)-al-(l) med et diamin med den generelle formel The process according to the invention for the production of said therapeutically active amines according to the above general formula or their salts is characterized by reacting (3-ionone or 4-[2,6,6-trimethyl-cyclohexen-(1)-yl]-2 -methyl-butene(2)-al-(1) with a diamine of the general formula

H-N-alkylen-Ri H-N-alkylene-Ri

i hvilken Ri betyr en tertiær aminogruppe, i nærvær av reduksjonsmidler, hvorpå det erholdte amin acyleres eller alkyleres og/ eller kan overføres i de normale eller kvaternære salter. in which Ri means a tertiary amino group, in the presence of reducing agents, whereupon the amine obtained is acylated or alkylated and/or can be transferred into the normal or quaternary salts.

Som reduksjonsmidler anvendes fortrinsvis katalytisk aktivert vannstoff. Al-kyleringen kan skje ved reduksjon av de tilsvarende N-acylforbindelser ved hjelp av litiumalummiumhydrid. N-acylderivatene på sin side utvinnes ved omsetning av ami-net med et organisk syreanhydrid eller et organisk syrehalogenid. På den annen side kan metyleringen av de først erholdte aminer også bevirkes f. eks. ved innvirkning av en formaldehyd-maursyre-blanding. Catalytically activated hydrogen is preferably used as reducing agents. The alkylation can take place by reduction of the corresponding N-acyl compounds using lithium aluminum hydride. The N-acyl derivatives, on the other hand, are recovered by reacting the amine with an organic acid anhydride or an organic acid halide. On the other hand, the methylation of the first obtained amines can also be effected, e.g. by exposure to a formaldehyde-formic acid mixture.

Oppfinnelsen skal beskrives ved de et-terfølgende eksempler uten å være begren-set til disse. The invention shall be described by the following examples without being limited to these.

Eksempel 1: Example 1:

155 g (0,8 molu (3-jonon og 214 g (1,85 mol) (3-dietylaminoetylamin oppløses i 400 cm<3> etylalkohol og hydreres i nærvær av en Raney-nikkel-katalysator ved en tem-peratur på 60° C og et trykk på 105 kg/cm<2>. Katalysatoren filtreres fra, alkoholen avdestilleres og den tilbakeblivende olje underkastes i vakuum en fraksjonert destillasjon, hvorved man får N<2>,N<2->dietyl-N'-(l-metyl-3-[2,6,6,-trimetyl-cykloheksen-(1)-yl-(1)]-propyl)-etylendiamin med ko-28 155 g (0.8 mol) of 3-ionone and 214 g (1.85 mol) of 3-diethylaminoethylamine are dissolved in 400 cm<3> of ethyl alcohol and hydrated in the presence of a Raney-nickel catalyst at a temperature of 60 ° C and a pressure of 105 kg/cm<2>. The catalyst is filtered off, the alcohol is distilled off and the remaining oil is subjected to a fractional distillation in vacuum, whereby N<2>,N<2->diethyl-N'-( 1-methyl-3-[2,6,6,-trimethyl-cyclohexene-(1)-yl-(1)]-propyl)-ethylenediamine with co-28

kepunkt 133° C/0,4 mm, n D= 1,4723. boiling point 133° C/0.4 mm, n D= 1.4723.

50 g (0,17 mol) av det slik erholdte diamin løses i 32,5 cm:! (0,6 mol) 90 pst.'s maursyre og 16,2 cm<:i> (0,19 mol) 35 pst.'s formaldehyd. Denne oppløsning oppvarmes til kokning under omrøring i 3 timer under tilbakeløp. Derpå konsentreres oppløsnin-gen i vakuum oppnådd ved hjelp av en vannstrålepumpe. Den sirupaktige rest gjøres sterkt alkalisk med 15 pst.'s kalium-hydrcksyd og blandingen ekstraheres derpå med eter. Eterekstraktet vaskes med vann og tørres med kaliumkarbonat. Eteren avdestilleres, og den tilbakeblivende olje underkastes en fraksjonert destillasjon, hvorved man får N<2>,N<2->dietyl-N<1->(l-metyl-3-[2,6,6-trimetyl-cykloheksen-(1)-yl-(1)]-propyl)-etylendiamin med kokepunkt 135° 50 g (0.17 mol) of the diamine thus obtained is dissolved in 32.5 cm:! (0.6 mole) 90 percent formic acid and 16.2 cm<:i> (0.19 mole) 35 percent formaldehyde. This solution is heated to boiling with stirring for 3 hours under reflux. The solution is then concentrated in a vacuum obtained by means of a water jet pump. The syrupy residue is made strongly alkaline with 15 per cent potassium hydroxide and the mixture is then extracted with ether. The ether extract is washed with water and dried with potassium carbonate. The ether is distilled off, and the remaining oil is subjected to a fractional distillation, whereby N<2>,N<2->diethyl-N<1->(1-methyl-3-[2,6,6-trimethyl-cyclohexene- (1)-yl-(1)]-propyl)-ethylenediamine with a boiling point of 135°

23 C/0,3 mm, n D = 1,4758. 23 C/0.3 mm, n D = 1.4758.

Eksempel 2: Example 2:

10 g (0,032 mol) N<2>,N<2->dietyl-N<<->metyl-ISP-(1 -metyl-3 - [2,6,6-trimetyl-cykloheksen-(l)-yl-(l)]-propyl)-etylendiamin . (erholdt ifølge angivelser i eksempel 1) løses i 100 cirr aceton, inneholdende 40 vektspst. me- 10 g (0.032 mol) N<2>,N<2->diethyl-N<<->methyl-ISP-(1-methyl-3-[2,6,6-trimethyl-cyclohexen-(1)-yl -(l)]-propyl)-ethylenediamine . (obtained according to the instructions in example 1) is dissolved in 100 cir acetone, containing 40 wt. me-

tylbromid. Oppløsningen las henstå ved værelsestemperatur. Etter 48 timer filtreres de dannede, hvite krystaller fra, vaskes med aceton og tørres. Man får på denne måte dimetobromidet av N<2>,N<2->dietyl-N'-metyl-N<1->(l-metyl-3-[2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] -propyl) -etylendiamin-dihydrat, som smelter etter omkrystallise-ringen fra acetonitril-eter ved 195—196° C (under spaltning). tyl bromide. Allow the solution to stand at room temperature. After 48 hours, the formed white crystals are filtered off, washed with acetone and dried. In this way, the dimethobromide of N<2>,N<2->diethyl-N'-methyl-N<1->(1-methyl-3-[2,6,6-trimethyl-cyclohexene- (1) -yl-(1)]-propyl)-ethylenediamine dihydrate, which melts after the recrystallization from acetonitrile ether at 195-196° C (under decomposition).

Eksempel 3. Example 3.

En oppløsning av 11,8 g (.0,04 mol) N2,N<2->dietyl-N<1->(l-metyl-3-[2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] -propyl) -etylen - diamin (erholdt ifølge avsnitt 1 i eksempel A solution of 11.8 g (.0.04 mol) N2,N<2->diethyl-N<1->(1-methyl-3-[2,6,6-trimethyl-cyclohexene-(1)- yl-(1) ] -propyl) -ethylene - diamine (obtained according to section 1 in Example

1) og 9,5 g (0,041 mol) difenylacetylklorid 1) and 9.5 g (0.041 mol) of diphenylacetyl chloride

i 200 cm<3> tørr benzol oppvarmes i 3 timer under tilbakeløp. Derpå avdestilleres benzolen og den tilbakeblivende gummiaktige masse gjøres alkalisk ved hjelp av vandig natriumkarbonat og ekstraheres med eter. Eterekstraktet vaskes med vann, tørres med natriumsulfat og eteren avdestilleres derpå. Den tilbakeblivende olje, som inneholder N^N-dietyl-N1 -dif enylacetyl-N' - (1-metyl-3 - [2,6,6-trimetyl-cykloheksen- (1) - yl-(1)]-propyl)-etylendiamin, løses i 100 cm<*> aceton, som inneholder 40 vektspst. metylbromid. Den slik erholdte oppløsning lagres i 48 timer og inndampes derpå til tørrhet, hvorpå man krystalliserer den tilbakeblivende, gule gummi fra etylacetat-petroleter. Det slik erholdte metobromid av in 200 cm<3> of dry benzene is heated for 3 hours under reflux. The benzene is then distilled off and the remaining gummy mass is made alkaline by means of aqueous sodium carbonate and extracted with ether. The ether extract is washed with water, dried with sodium sulphate and the ether is then distilled off. The residual oil, containing N^N-diethyl-N1-diphenylacetyl-N'-(1-methyl-3-[2,6,6-trimethyl-cyclohexene-(1)-yl-(1)]-propyl )-ethylenediamine, is dissolved in 100 cm<*> acetone, which contains 40 wt. methyl bromide. The solution thus obtained is stored for 48 hours and then evaporated to dryness, after which the remaining yellow gum is crystallized from ethyl acetate-petroleum ether. The methobromide thus obtained of

N2,N2-dietyl-N> -dif enylacetyl-N1 - (1-metyl-3- [2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] - N2,N2-diethyl-N> -diphenylacetyl-N1 - (1-methyl-3- [2,6,6-trimethyl-cyclohexene- (1) -yl-(1) ] -

propyl)-etylendiamin smelter ved 144— 146° C. propyl)-ethylenediamine melts at 144— 146° C.

Eksempel 4: Example 4:

En oppløsning av 11,8 g (0,04 mol) N<2>,N<2->dietyl-N'-(l-metyl-3-[2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] -propyl-etylendiamin (erholdt ifølge eksempel 1) og 9,5 g A solution of 11.8 g (0.04 mol) N<2>,N<2->diethyl-N'-(1-methyl-3-[2,6,6-trimethyl-cyclohexene-(1)- yl-(1)]-propyl-ethylenediamine (obtained according to Example 1) and 9.5 g

(0,041 mol) difenylacetylklorid i 200 cm'<! >tørr benzol oppvarmes i 3 timer under til-bakeløp. Benzolen destilleres derpå av og den tilbakeblivende gummi gjøres alkalisk ved hjelp av vandig natriumkarbonat og ekstraheres med eter. Eterekstrakten vaskes med vann, tørres med natriumsulfat og behandles med bromvannstoffgass inntil produktet reagerer kongosurt. Derpå avdestilleres eteren og den tilbakeblivende N2,N2-dietyl-N' -dif enyl-acetyl-N1 - (1 - m etyl -3 - [2,6,6 -tr imetyl-cykloheksen - (1) - yl- (1) ] -propyl) -etylendiamin-hydrobromid med smeltepunkt 180—181° C krystalliseres fra etanol-eter. (0.041 mole) of diphenylacetyl chloride in 200 cm'<! >dry benzene is heated for 3 hours under reflux. The benzene is then distilled off and the remaining gum made alkaline with aqueous sodium carbonate and extracted with ether. The ether extract is washed with water, dried with sodium sulfate and treated with hydrogen bromine gas until the product reacts with Congo acid. Then the ether is distilled off and the remaining N2,N2-diethyl-N'-diphenyl-acetyl-N1 - (1 - methyl -3 - [2,6,6 -trimethyl-cyclohexene - (1) - yl - (1 ) ] -propyl) -ethylenediamine hydrobromide with a melting point of 180-181° C is crystallized from ethanol-ether.

Eksempel 5: Example 5:

20 g (0,035 mol) N<2>,N<2->dietyl-INP-dife-nylacetyl-Ni<->(l-metyl-3-[2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] -propyl) -etylendiamin-hydrobromid (erholdt ifølge eksempel 4) suspenderes i vann og denne suspensjon tilsettes overskytende natriumkarbonat, hvorpå blandingen under kraftig omrøring ekstraheres med eter. Eterekstraktet vaskes med vann og tørres med natriumsulfat, hvorpå man avdestillerer eteren. Den tilbakeblivende olje løses i 100 cm'<!> acetonitril, tilsettes 7,6 g (0,035 mol) p-nitrobenzylbromid, og oppløsningen oppvarmes under tilbakeløp i 24 timer. Opp-løsningen kjøles derpå, de flyktige bestand-deler avdestilleres og det tilbakeblivende gummiaktige produkt krystalliseres fra etanol-eter. Det slik erholdte N<2->p-nitro-benzyl-bromid av N^N—dietyl-Ni<->difenyl-acetyl-N1- (l-metyl-3- [2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] -propyl) -etylendiamin 20 g (0.035 mol) N<2>,N<2->diethyl-INP-diphen-nylacetyl-Ni<->(1-methyl-3-[2,6,6-trimethyl-cyclohexene- (1)- yl-(1)]-propyl)-ethylenediamine hydrobromide (obtained according to example 4) is suspended in water and excess sodium carbonate is added to this suspension, after which the mixture is extracted with ether while vigorously stirring. The ether extract is washed with water and dried with sodium sulphate, after which the ether is distilled off. The remaining oil is dissolved in 100 cm3 of acetonitrile, 7.6 g (0.035 mol) of p-nitrobenzyl bromide are added, and the solution is heated under reflux for 24 hours. The solution is then cooled, the volatile constituents are distilled off and the remaining gummy product is crystallized from ethanol-ether. The thus obtained N<2->p-nitro-benzyl bromide of N^N—diethyl-Ni<->diphenyl-acetyl-N1-(1-methyl-3-[2,6,6-trimethyl-cyclohexene- (1) -yl-( (1) ] -propyl) -ethylenediamine

smelter ved 127—128° C. melts at 127-128° C.

Eksempel 6: Example 6:

206 g (1 mol.) 4-[2,6,6-trimetyl-cykloheksen- ( 1) -yl- (1) ] -2-metylbuten- (2) al-(1) og 120 g (1,03 mol) p-dietylaminoetylamin, oppløst i 400 cm<3> etylalkohol, hydreres i nærvær av en Raney-nikkel-katalysator ved et trykk på 105 kg/cm- og en tem-peratur på 150° C. Derpå filtreres katalysatoren fra, alkoholen avdestilleres og den tilbakeblivende olje fraksjoneres i vakuum, hvorved man får N<1->(2-metyl-4-[2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] -butyl) - 206 g (1 mol.) 4-[2,6,6-trimethyl-cyclohexene-(1)-yl-(1)]-2-methylbutene-(2)al-(1) and 120 g (1.03 mol) p-diethylaminoethylamine, dissolved in 400 cm<3> ethyl alcohol, is hydrogenated in the presence of a Raney nickel catalyst at a pressure of 105 kg/cm and a temperature of 150° C. The catalyst is then filtered off, the alcohol is distilled off and the remaining oil is fractionated in vacuum, whereby N<1->(2-methyl-4-[2,6,6-trimethyl-cyclohexene- (1)-yl-(1) ]-butyl) -

N<2>,N<2->dietyletylendiamin med kokepunkt 140° C/0,07 mm, n D = 1,4783. N<2>,N<2->diethylethylenediamine with boiling point 140° C/0.07 mm, n D = 1.4783.

Behandles en del av det slik erholdte produkt med en oppløsning av oksalsyre i aceton så får man det tilsvarende dioksalat i krystallinsk form, hvilket etter omkrystallisering fra vann-metylalkohol-aceton smelter ved 201—202° C (under spaltning). If part of the product obtained in this way is treated with a solution of oxalic acid in acetone, the corresponding dioxalate is obtained in crystalline form, which after recrystallization from water-methyl alcohol-acetone melts at 201-202° C (under decomposition).

Eksempel 7: Example 7:

61,6 g (0..2 mol N'-(2-metyl-4-[2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] -butyl) - 61.6 g (0..2 mol N'-(2-methyl-4-[2,6,6-trimethyl-cyclohexen-(1)-yl-(1)]-butyl) -

N<2>,N<2->dietyletylendiamin løses i 26 cm3 (0,5 mol) 90 pst.'s maursyre og denne oppløs-ning tilsettes 19 cm3 (0,22 mol) 35 pst.'s formaldehyd. Oppløsningen oppvarmes under omrøring 3 timer på dampbad og overskuddet av formaldehyd og maursyre avdestilleres. Den tilbakeblivende olje gjøres sterkt alkalisk med 30 pst.'s natrium-hydroksyd og ekstraheres med eter. Eterekstraktet vaskes med vann, tørres med kaliumkarbonat og eteren avdestilleres så. Den tilbakeblivende olje underkastes i vakuum en fraksjonert destillasjon, hvorved man får N<1->metyl-Nl<->(2-metyl-4-[2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] -butyl) - N<2>,N<2->dietyletylendiamin med kokepunkt N<2>,N<2->diethylethylenediamine is dissolved in 26 cm3 (0.5 mol) 90% formic acid and 19 cm3 (0.22 mol) 35% formaldehyde is added to this solution. The solution is heated with stirring for 3 hours on a steam bath and the excess of formaldehyde and formic acid is distilled off. The remaining oil is made strongly alkaline with 30% sodium hydroxide and extracted with ether. The ether extract is washed with water, dried with potassium carbonate and the ether is then distilled off. The remaining oil is subjected to a fractional distillation in vacuum, whereby N<1->methyl-Nl<->(2-methyl-4-[2,6,6-trimethyl-cyclohexene- (1)-yl- (1 ) ] -butyl) - N<2>,N<2->diethylethylenediamine with boiling point

27 27

134° C/0,07 mm, n ^ = 1,4770. 134°C/0.07 mm, n ^ = 1.4770.

En del av den slik erholdte forbindelse behandles med en oppløsning av oksalsyre 1 aceton, hvorved man får det tilsvarende dioksalat, som, omkrystallisert fra metyl-alkoholaceton, smelter ved 183—134° C (under spaltning). Part of the compound thus obtained is treated with a solution of oxalic acid 1 acetone, whereby the corresponding dioxalate is obtained, which, recrystallized from methyl alcohol acetone, melts at 183-134° C (under decomposition).

Eksempel 8: Example 8:

16 g (0,05 mol) N1-rnetyl-N1-(2-metyl-4- [2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] - butyl)-N<2>,N<2->dietyletylendiamin (erholdt ifølge eksempel 7) behandles med 100 cm:: aceton, inneholdende 40 vektspst. metylbromid, hvorpå denne blanding lagres i 48 timer ved værelsestemperatur. Derpå inndampes den oppståtte oppløsning til tørr-het og den tilbakeblivende gummi krystalliseres fra isopropanol-eter. Dimetobromidet av Nl<->metyl-N<1->(2-metyl-4-[2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] -butyl) - N<2>,N<2->dietyletylendiamin-sesquihydrat, som fås på denne måte, smelter ved 65— 66° C, hvorved sintring skjer ved 61° C. 16 g (0.05 mol) N1-methyl-N1-(2-methyl-4-[2,6,6-trimethyl-cyclohexen- (1)-yl-(1)]-butyl)-N<2> ,N<2->diethylethylenediamine (obtained according to example 7) is treated with 100 cm:: acetone, containing 40 wt. methyl bromide, after which this mixture is stored for 48 hours at room temperature. The resulting solution is then evaporated to dryness and the remaining gum is crystallized from isopropanol-ether. The dimethobromide of Nl<->methyl-N<1->(2-methyl-4-[2,6,6-trimethyl-cyclohexen-(1)-yl-(1)]-butyl)-N<2>, N<2->diethylethylenediamine sesquihydrate, which is obtained in this way, melts at 65-66° C, whereby sintering takes place at 61° C.

Eksempel 9: Example 9:

Man tilsetter en oppløsning av 38,4 g (0,2 mol) (3-jonon og 23 g (0,2 mol) 3-dimetylaminopropylamin i 150 cm" etylalkohol Raney-nikkel-katalysator i en mengde av 2 teskjeer. Blandingen hydreres ved 150° C og 105 kg/cm<2>, hvorpå katalysatoren filtreres fra, etylalkoholen avdestilleres og den tilbakeblivende olje fraksjoneres i vakuum, hvorved man får N<1->(l-metyl-3-[2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] -propyl) - N<2>,N<2->dimetyl-l,3-propylendiamin med A solution of 38.4 g (0.2 mol) (3-ionone and 23 g (0.2 mol) 3-dimethylaminopropylamine in 150 cm" of ethyl alcohol Raney-nickel catalyst is added in an amount of 2 teaspoons. The mixture is hydrated at 150° C and 105 kg/cm<2>, after which the catalyst is filtered off, the ethyl alcohol is distilled off and the remaining oil is fractionated in vacuum, whereby N<1->(l-methyl-3-[2,6,6- trimethyl-cyclohexene-(1)-yl-(1)]-propyl)-N<2>,N<2->dimethyl-1,3-propylenediamine with

25 kokepunkt 120° C/0,1 mm, nD = 1,4743. 25 boiling point 120° C/0.1 mm, nD = 1.4743.

En del av det slik erholdte produkt behandles med en oppløsning av oksalsyre i aceton, hvorved man får det tilsvarende dioksalat-hemihydrat i krystallinsk form, som smelter etter omkrystallisering fra 95 pst.'s etanol ved 172—173° C (under spaltning) . Part of the product thus obtained is treated with a solution of oxalic acid in acetone, whereby the corresponding dioxalate hemihydrate is obtained in crystalline form, which melts after recrystallization from 95% ethanol at 172-173° C (with decomposition).

Eksempel 10: 38,4 g (0,2 mol) fj-jonon og 26 g (0,2 mol) 3-dietylaminopropylamin omsettes etter angivelsene i eksempel 9, hvorved man får N1 -(l-metyl-3-[2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] -propyl) -N<2>,N<2->dietyl-1,3-propylendiamin med kokepunkt 122— Example 10: 38.4 g (0.2 mol) fj-ionone and 26 g (0.2 mol) 3-diethylaminopropylamine are reacted according to the instructions in example 9, whereby N1 -(1-methyl-3-[2, 6,6-trimethyl-cyclohexene-(1)-yl-(1)]-propyl)-N<2>,N<2->diethyl-1,3-propylenediamine with boiling point 122—

125° C/0,08 mm, n ^ = 1,4715. 125°C/0.08 mm, n ^ = 1.4715.

Behandles en del av dette produkt med en oppløsning av oksalsyre i aceton så får man det tilsvarende dioksalat, som fås i krystallinsk form og etter omkrystallisering fra vann-acetonitril under spaltning smelter ved 178—179° C. If part of this product is treated with a solution of oxalic acid in acetone, the corresponding dioxalate is obtained, which is obtained in crystalline form and after recrystallization from water-acetonitrile during cleavage melts at 178-179°C.

Eksempel 11: Example 11:

38,4 (0,2 mol) (3-jonon og 37,2 g (0,2 mol) 3-dibutylaminopropylamin omsettes med hverandre på den i eksempel 9 beskrevne måte, hvorved man får N'-(l-metyl-3- [2,6,6-trimetyl-cykloheksen- (1) - 38.4 (0.2 mol) (3-ionone and 37.2 g (0.2 mol) 3-dibutylaminopropylamine are reacted with each other in the manner described in example 9, whereby N'-(1-methyl-3 - [2,6,6-trimethyl-cyclohexene-(1)-

yl- (1) ] -propyl) -N2,N2-dibutyl-1,3 -propylen-diamin med kokepunkt 150—153° C/0,06 yl-(1)]-propyl)-N2,N2-dibutyl-1,3-propylene-diamine with boiling point 150-153° C/0.06

28 28

mm, n D = 1.4728. mm, n D = 1.4728.

Behandles en del av det slik erholdte produkt med en oppløsning av oksalsyre i aceton, så får man det tilsvarende dioksalat i krystallinsk form, som etter omkrystallisering fra 95 pst.'s etylalkohol smelter ved 161—163° C. If part of the product obtained in this way is treated with a solution of oxalic acid in acetone, the corresponding dioxalate is obtained in crystalline form, which after recrystallization from 95% ethyl alcohol melts at 161-163°C.

Eksempel 12: Example 12:

38,4 g (0,2 mol) (3-jonon og 28,4 g (0,2 mol) N-aminopropyl-morfolin omsettes med hverandre etter den i eksempel 9 beskrevne metode under dannelse av N-(l-metyl-3-[2,6,6-trimetyl-cykloheksan-(l)-yl- (1) ] -propyl) -3- (4-morf olinyl) -propyl-26 amin med kokepunkt 155—158° C, nD = 38.4 g (0.2 mol) (3-ionone and 28.4 g (0.2 mol) N-aminopropyl-morpholine are reacted with each other according to the method described in example 9 to form N-(1-methyl- 3-[2,6,6-trimethyl-cyclohexane-(1)-yl-(1)]-propyl)-3-(4-morpholinyl)-propyl-26-amine with boiling point 155-158° C, nD =

1,4859. 1.4859.

En del av denne forbindelse behandles med en oppløsning av oksalsyre i aceton og gir derved det tilsvarende dioksalat i krystallinsk form, som etter omkrystallisering fra 80 pst.'s etylalkohol smelter ved 186— 187° C. Part of this compound is treated with a solution of oxalic acid in acetone and thereby gives the corresponding dioxalate in crystalline form, which after recrystallization from 80% ethyl alcohol melts at 186-187°C.

Eksempel 13: Example 13:

41,2 (0,2 mol) 4-[2,6,6-trimetyl-cykloheksen- (1) -yl] -2-metylbuten- (2) -al- (1) og 23 g (0,2 mol) 3-dimetylamino-propylamin bringes til reaksjon med hverandre på den i eksempel 9 beskrevne måte, hvorved man får N1 -(2-metyl-4-[2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] -butyl) -N-',N--dimetyl-1,3-propandiamin med kokepunkt 130—133° 26 C/0,1 mm, m D = 1,4772. 41.2 (0.2 mol) 4-[2,6,6-trimethyl-cyclohexen-(1)-yl]-2-methylbuten-(2)-al-(1) and 23 g (0.2 mol ) 3-dimethylamino-propylamine is reacted with each other in the manner described in example 9, whereby obtains N1 -(2-methyl-4-[2,6,6-trimethyl-cyclohexen- (1)-yl-(1) ]-butyl)-N-',N--dimethyl-1,3-propanediamine with boiling point 130-133° 26 C/0.1 mm, m D = 1.4772.

Behandler man en del av det slik erholdte produkt med en oppløsning av oksalsyre i aceton så får man det tilsvarende dioksalat i krystallinsk form, som etter omkrystallisering fra 80 pst's etanol-etanol smelter ved 201—203° C (under spaltning). If you treat part of the product obtained in this way with a solution of oxalic acid in acetone, you get the corresponding dioxalate in crystalline form, which after recrystallization from 80% ethanol-ethanol melts at 201-203°C (under decomposition).

Eksempel 14: Example 14:

9,1 g (0,03 mol) N'-(2-metyl-4-[2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] -butyl) - N<2>,N<2->dimetyl-1,3-propyldiamin (erholdt ifølge angivelser i eksempel 13) løses i 6 cm<:>) (0,1 mol) 90 pst.'s maursyre, og denne oppløsning tilsettes 3 cm:! (0,034 mol) 35 pst.'s formaldehyd. Oppløsningen oppvarmes under omrøring på dampbad 3 timer og derpå avdestilleres overskuddet av formaldehyd og maurs<y>re. Den tilbakeblivende olje gjøres sterkt alkalisk med 30 pst.'s na-triumhydroksyd og ekstrahéres med eter. Eterekstraktet vaskes med vann og tørres med kaliumkarbonat, hvorpå eteren avdestilleres. En olje som består av N'-metyl-N<1->(2-metyl-4-[2,6,6-trimetyl-cykloheksen-(1) -yl- (1) ] -butyl) -N<2>,N<2>-dimetyl-l,3-pro-pylendiamin med kokepunkt 127—129° C/ 0,3 mm blir tilbake, behandles samme med en oppløsning av oksalsyre i aceton så får man det tilsvarende dioksalat, som etter omkrystallisering fra metylalkohol smelter ved 190—191° C (under spaltning). 9.1 g (0.03 mol) N'-(2-methyl-4-[2,6,6-trimethyl-cyclohexen-(1)-yl-(1)]-butyl)-N<2>, N<2->dimethyl-1,3-propyldiamine (obtained according to instructions in example 13) is dissolved in 6 cm<:>) (0.1 mol) of 90 percent formic acid, and this solution is added to 3 cm:! (0.034 mol) 35 percent formaldehyde. The solution is heated with stirring on a steam bath for 3 hours and then the excess of formaldehyde and antacid is distilled off. The remaining oil is made strongly alkaline with 30% sodium hydroxide and extracted with ether. The ether extract is washed with water and dried with potassium carbonate, after which the ether is distilled off. An oil consisting of N'-methyl-N<1->(2-methyl-4-[2,6,6-trimethyl-cyclohexen-(1)-yl-(1)]-butyl)-N<2 >,N<2>-dimethyl-1,3-propylenediamine with a boiling point of 127-129° C/ 0.3 mm remains, the same is treated with a solution of oxalic acid in acetone and the corresponding dioxalate is obtained, which after recrystallization from methyl alcohol melts at 190-191° C (under decomposition).

Eksempel 15: Example 15:

41,2 g (0,2 mol) 4-[2,6,6-trimetyl-cykloheksen- (1) -yl] -2-metylbuten- (2) -al- (1) og 26 g (0.2 mol) 3-dietylamino-propylamin omsettes med hverandre ifølge den i eksempel 9 beskrevne metode, hvorved man får N'-(2-metyl-4-[2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] -butyl) -N<2>,N<2->dietyl-1,3-propylendiamin med kokepunkt 145— 41.2 g (0.2 mol) 4-[2,6,6-trimethyl-cyclohexen-(1)-yl]-2-methylbuten-(2)-al-(1) and 26 g (0.2 mol) 3-diethylamino-propylamine is reacted with each other according to the method described in example 9, whereby N'-(2-methyl-4-[2,6,6-trimethyl-cyclohexen-(1)-yl-(1)] is obtained -butyl) -N<2>,N<2->diethyl-1,3-propylenediamine with boiling point 145—

147° C, n ^ = 1,4778. 147°C, n ^ = 1.4778.

Behandles en del av det slik erholdte stoff med en oppløsning av oksalsyre i aceton så får man det tilsvarende dioksalat i krystallinsk form, som etter omkrystallisering fra 80 pst.'s vanndig etanol smelter ved 182—183° C (under spaltning). If part of the material obtained in this way is treated with a solution of oxalic acid in acetone, the corresponding dioxalate is obtained in crystalline form, which after recrystallization from 80% aqueous ethanol melts at 182-183° C (under decomposition).

Eksevipel 16: Exodus 16:

9,7 g (0,3 mol) N'-(2-metyl-4-[2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] -butyl) - N-,N--dietyl -1,3-propylendiamin (erholdt ifølge eksempel 15), 6 cm'<!> (0,1 mol) 90 pst.'s maursyre og 3 cm<:i> (0,034 mol) 35 pst.'s formaldehyd omsettes på den i eksempel 15 beskrevne måte, hvorved man får ISP-metyl-N'-(2-metyl-4-[2,G,6-trimetyl-cykloheksen-(1) -yl- (1) ] -butyl) -N-,N-'-dietyl-l,3-propy-lendiamin-dioksalat, som etter omkrystallisering fra vann-etylalkohol smelter ved 198-199° C (under spaltning). 9.7 g (0.3 mol) N'-(2-methyl-4-[2,6,6-trimethyl-cyclohexen-(1)-yl-(1)]-butyl)-N-,N- -diethyl-1,3-propylenediamine (obtained according to Example 15), 6 cm'<!> (0.1 mol) 90% formic acid and 3 cm<:i> (0.034 mol) 35% formaldehyde is reacted in the manner described in example 15, which gives ISP-methyl-N'-(2-methyl-4-[2,G,6-trimethyl-cyclohexene-(1)-yl-(1)]-butyl) -N-,N-'-diethyl-1,3-propylene-diamine dioxalate, which after recrystallization from water-ethyl alcohol melts at 198-199° C (under decomposition).

Eksempel 17: Example 17:

41,2 g (0,2 mol) 4-[2,6,6-trimetyl-cykloheksen- (1) -yl] -2-metylbuten- (2) -al- (1) og 37,2 g (0,2 mol) 3-dibutylamino-propylamin omsettes med hverandre ifølge angivelser i eksempel 9, hvorved man får N'~ (2-metyl-4-[2,6,6-trimetyl-cykloheksen-(1) -yl- (1) ] -butyl) -N<2>,N<2->dibutyl-l,3-propy-lendiamin med kokepunkt 155—158° C/0,06 28 mm, n D = 1,4758. •Behandler man en del av dette produkt med en oppløsning av oksalsyre i aceton så får man etter omkrystallisering fra 60 pst.'s etylalkohol det tilsvarende dioksalat i krystallinsk form med smeltepunkt 187— 188° C (under spaltning). 41.2 g (0.2 mol) 4-[2,6,6-trimethyl-cyclohexen-(1)-yl]-2-methylbuten-(2)-al-(1) and 37.2 g (0 .2 mol) of 3-dibutylamino-propylamine are reacted with each other according to the instructions in example 9, whereby N'~ (2-methyl-4-[2,6,6-trimethyl-cyclohexen-(1)-yl- (1 ) ] -butyl) -N<2>,N<2->dibutyl-1,3-propylenediamine with boiling point 155-158° C/0.06 28 mm, n D = 1.4758. •If you treat part of this product with a solution of oxalic acid in acetone, you get, after recrystallization from 60% ethyl alcohol, the corresponding dioxalate in crystalline form with a melting point of 187-188° C (under decomposition).

Eksempel 18: Example 18:

41.2 g (0,2 mol) 4-[2,6,6-trimetyl-cykloheksen- (1) -yl] -2-metylbuten- (2) -al- (1) - og 31,2 g (0,2 mol) 5-dietylamino-2-amino-pentan omsettes med hverandre på den i eksempel 9 beskrevne måte, hvorved man får N1 ,N'-dietyl-4-metyl-N--(2-metyl-4-[2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] - butyl)-1,4-butylendiamin med kokepunkt 41.2 g (0.2 mol) 4-[2,6,6-trimethyl-cyclohexen-(1)-yl]-2-methylbuten-(2)-al-(1)- and 31.2 g (0, 2 mol) of 5-diethylamino-2-amino-pentane are reacted with each other in the manner described in example 9, whereby N1,N'-diethyl-4-methyl-N-(2-methyl-4-[2, 6,6-trimethyl-cyclohexene-(1)-yl-(1)]- butyl)-1,4-butylenediamine with boiling point

25 25

142° C/0,07 mm, n D = 1,4783. 142° C/0.07 mm, n D = 1.4783.

Behandles 1 del av den slik erholdte forbindelse med en oppløsning av oksalsyre i aceton, og det slik frembragte dioksalat, som fås i krystallinsk form, omkrystallise-res fra 95 pst.'s etanol, så smelter det ved 168—170° C (under spaltning). If 1 part of the compound thus obtained is treated with a solution of oxalic acid in acetone, and the dioxalate thus produced, which is obtained in crystalline form, is recrystallized from 95 percent ethanol, it melts at 168-170° C (below cleavage).

Eksempel 19: Example 19:

10.3 g (0,03 mol) N',N'-dietyl-4-metyl-N;;- (2-metyl-4- [2,6,6-trimetyl-cykloheksen-(1)-yl-(1) ]-butyl-l,4-butylendiamin (erholdt ifølge eksempel 17), 6 cm'<1> (0,1 mol) 10.3 g (0.03 mol) N',N'-diethyl-4-methyl-N;;-(2-methyl-4-[2,6,6-trimethyl-cyclohexen-(1)-yl-(1 ) ]-butyl-1,4-butylenediamine (obtained according to Example 17), 6 cm'<1> (0.1 mol)

90 pst.'s maursyre og 3 cm:! (0,034 mol) 35 90 percent formic acid and 3 cm:! (0.034 mol) 35

pst.'s formaldehyd, omsettes med hverandre på den i eksempel 14 beskrevne måte, hvorved man får N<l>,N<l->dietyl-N--metyl-N--(2-metyl-4- [2,6,6-trimetyl-cykloheksen- (1) - yl-(l)]-butyl)-l,4-pentylendiamin- dioksalat med smeltepunkt 138—140° C (etter omkrystallisering fra etyl-alkohol-aceton). pst.'s formaldehyde, are reacted with each other in the manner described in example 14, whereby N<l>,N<l->diethyl-N--methyl-N--(2-methyl-4- [2, 6,6-trimethyl-cyclohexene-(1)-yl-(l)]-butyl)-1,4-pentylenediamine dioxalate with melting point 138-140° C (after recrystallization from ethyl alcohol-acetone).

Eksempel 20: Example 20:

41,2 g (0,2 mol) 4-[2,6,6-trimetyl-cykio-heksen-(1)-yl]-2-metylbuten-(2)-al-(1) og 28,4 g (0,2 mol) N-amino-propyl-morfoiin omsettes med hverandre ifølge den i eksempel 9 beskrevne metode, hvorved man får N-(2-metyl-4-[2,6,6-trimetyl-cyklohekséti-(1) -yl- (1) ] -butyl) -3- (4-morf olinyl) propylamin med kokepunkt 157—160° C/ 41.2 g (0.2 mol) 4-[2,6,6-trimethyl-cyclo-hexen-(1)-yl]-2-methylbuten-(2)-al-(1) and 28.4 g (0.2 mol) of N-amino-propyl-morphoin are reacted with each other according to the method described in example 9, whereby N-(2-methyl-4-[2,6,6-trimethyl-cyclohexeti-(1)) is obtained -yl-(1) ] -butyl) -3-(4-morpholinyl)propylamine with a boiling point of 157—160° C/

25 25

0,1 mm, n D = 1,4877. 0.1 mm, n D = 1.4877.

Behandler man en del av denne forbindelse med en oppløsning av oksalsyre i aceton så får man det tilsvarende dioksalat i krystallinsk form, som etter omkrystallisering fra metylalkohol smelter ved 171—173° C (under spaltning).. If you treat part of this compound with a solution of oxalic acid in acetone, you get the corresponding dioxalate in crystalline form, which after recrystallization from methyl alcohol melts at 171-173° C (with decomposition).

Eksempel 21: Example 21:

10 g (0,03 mol) N-(2-metyl-4-[2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] -butyl) - 3- (4-morfolinyl)propylamin (erholdt ifølge eksempel 20), 6 cm:! (0,1 mol) 90 pst.'s maursyre og 3 cm-'<1> (0,034 mol) 35 pst.'s formaldehyd omsettes med hverandre ifølge angivelser i eksempel 14, hvorved man får N-etyl-N-(2-metyl-4-[2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] -butyl) -3- [2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] -butyl) -3- (4-morfolinyl) -proylamin-dioksalat med smeltepunkt 197—198° C (under spaltning) etter omkrystallisering fra 80 pst.'s etyl-alkohol. 10 g (0.03 mol) N-(2-methyl-4-[2,6,6-trimethyl-cyclohexen-(1)-yl-(1)]-butyl)-3-(4-morpholinyl)propylamine (obtained according to example 20), 6 cm:! (0.1 mol) 90 percent formic acid and 3 cm-'<1> (0.034 mol) 35 percent formaldehyde are reacted with each other according to the instructions in example 14, whereby N-ethyl-N-(2 -methyl-4-[2,6,6-trimethyl-cyclohexene-(1)-yl-(1)]-butyl)-3-[2,6,6-trimethyl-cyclohexene-(1)-yl-( 1) ]-butyl)-3-(4-morpholinyl)-propylamine dioxalate with melting point 197-198° C (under decomposition) after recrystallization from 80% ethyl alcohol.

Eksempel 22. Example 22.

40 g (0,082 mol) N<1->metyl-N<1->(2-metyl-4- [2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] butyl) -N-,N--dimetyl-l,3-propylendiamin-dioksalat (erholdt ifølge eksempel 14) suspenderes i vann og tilsettes overskytende natriumkarbonat, hvorpå den slik oppståtte blanding ekstraheres under kraftig omrøring. Eterekstraktet vaskes med vann, tørres med natriumsulfat og eteren destilleres av. Den tilbakeblivende olje løses i 15 cm" aceton og tilsettes derpå ytterligere 40 g (0.082 mol) N<1->methyl-N<1->(2-methyl-4-[2,6,6-trimethyl-cyclohexene-(1)-yl-(1)]butyl)-N -,N--dimethyl-1,3-propylenediamine dioxalate (obtained according to example 14) is suspended in water and excess sodium carbonate is added, after which the resulting mixture is extracted with vigorous stirring. The ether extract is washed with water, dried with sodium sulphate and the ether is distilled off. The remaining oil is dissolved in 15 cm" of acetone and then further added

250 cm<:i> aceton, inneholdende 40 vektspst. metylbromid. Denne oppløsning røres i 18 timer ved værelsestemperatur. De dan- 250 cm<:i> acetone, containing 40 wt. methyl bromide. This solution is stirred for 18 hours at room temperature. They dan-

nede krystaller filtreres fra og omkrystal- down crystals are filtered off and recrystallized

liseres fra acetonitril. På denne måte får man bis(metobromidet) av N<1->2-metyl-4-[2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] - is lysed from acetonitrile. In this way one obtains the bis(methobromide) of N<1->2-methyl-4-[2,6,6-trimethyl-cyclohexen- (1)-yl-(1) ] -

butyl) -N^N<2>,N<2->trimetyl-l,3-propylendi- butyl) -N^N<2>,N<2->trimethyl-1,3-propylenedi-

amin, som smelter ved 219—220° C (under spaltning) (etter foroppvarrhing på 3 gra- amine, which melts at 219—220° C (under decomposition) (after preheating of 3 gra-

der pr. minutt til 180° C). there per minute to 180° C).

Eksempel 23. Example 23.

Ifølge angivelser i eksempel 14 omset- According to the information in example 14, turnover

tes 43,9 g (0,16 mol) N<1->(l-metyl-3-[2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] -propyl) - N<2>,N<2->dimetyl-l,3-propylendiamin (beskre- tes 43.9 g (0.16 mol) N<1->(1-methyl-3-[2,6,6-trimethyl-cyclohexene-(1)-yl-(1)]-propyl) - N< 2>,N<2->dimethyl-1,3-propylenediamine (describe

vet i eksempel 9), 31,2 cm<2> (0,52 mol) 90 know in example 9), 31.2 cm<2> (0.52 mol) 90

pst.'s maursyre og 16 cm<:i> (0,18 mol) 35 pst.'s formic acid and 16 cm<:i> (0.18 mol) 35

pst.'s formaldehyd med hverandre hvorved man får N'-( l-metyl-3-[2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] -propyl) -N1 ,N2,N2-trimetyl-l,3-propylendiamin-dioksalat med smeltepunkt 226—227° C (under spaltning) pst.'s formaldehyde with each other, thereby obtaining N'-(1-methyl-3-[2,6,6-trimethyl-cyclohexen- (1)-yl-(1)]-propyl)-N1,N2,N2 -trimethyl-1,3-propylenediamine dioxalate with melting point 226-227° C (under decomposition)

etter krystallisering fra 80 pst.'s etylalko- after crystallization from 80 percent ethyl alcohol

hol. hol.

Eksempel 24. Example 24.

Ifølge angivelser i eksempel 22 omset- According to the information in example 22, turnover

tes 31,5 g (0,107 mol) N<1->(l-metyl-3-[2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] -propyl) - N\N<2>,N<2->trimetyl-l,3-propylendiamin og overskytende metylbromid i aceton med hverandre, hvorved man får bis(meto-bromidet) av N1 -(l-metyl-3-[2,6,6-trimetyl-cykloheksen- ( 1) -yl- (1) ] -propyl) -N1 ,N2, N2-trimetyl-1,3-propylendiamin-monohy- 31.5 g (0.107 mol) N<1->(1-methyl-3-[2,6,6-trimethyl-cyclohexene- (1)-yl-(1)]-propyl) - N\N< 2>,N<2->trimethyl-1,3-propylenediamine and excess methyl bromide in acetone with each other, whereby the bis(metho-bromide) of N1 -(1-methyl-3-[2,6,6-trimethyl -cyclohexene-(1)-yl-(1)]-propyl)-N1,N2,N2-trimethyl-1,3-propylenediamine-monohy-

drat med smeltepunkt 202—204° C (under spaltning og etter krystallisering fra ace- drate with a melting point of 202—204° C (during cleavage and after crystallization from ace-

tonitril). tonitrile).

Eksempel 25. Example 25.

tes 26,2 g (0,081 mol) N-(l-metyl-3-[2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] -propyl) - 3-(4-morfolinyl)-propylamin (ifølge ek- tes 26.2 g (0.081 mol) N-(1-methyl-3-[2,6,6-trimethyl-cyclohexen-(1)-yl-(1)]-propyl)-3-(4-morpholinyl) -propylamine (according to ec-

sempel 12), 16,2 cm3 (0,27 mol) 90 pst.'s maursyre og 8,1 cm<3> (0,92 mol) 35 pst.'s formaldehyd med hverandre, hvorved man får N-metyl-N-(l-metyl-3-[2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] -propyl) -3- (4-morfolinyl)-propylamin-dioksalat med example 12), 16.2 cm3 (0.27 mol) 90% formic acid and 8.1 cm<3> (0.92 mol) 35% formaldehyde with each other, whereby N-methyl- N-(1-methyl-3-[2,6,6-trimethyl-cyclohexen-(1)-yl-(1)]-propyl)-3-(4-morpholinyl)-propylamine dioxalate with

smeltepunkt 193—194° C (under spaltning) melting point 193-194° C (under decomposition)

etter utkrystallisering fra 80 pst.'s etyl- after crystallization from 80 percent ethyl

alkohol. alcohol.

Eksempel 26. Example 26.

Det arbeides som etter metoden i ek- It works as per the method in ek-

sempel 22, hvorved 10 g (0,03 mol) N-metyl-N-( l-metyl-3-[2,6,6-trimetyl-cykloheksen - sample 22, whereby 10 g (0.03 mol) of N-methyl-N-(1-methyl-3-[2,6,6-trimethyl-cyclohexene -

(1) -yl- (1) ] -propyl) -3- (4-morf olinyl) - (1) -yl-( (1) ] -propyl) -3-(4-morpholinyl) -

propylamin og overskytende metylbromid i aceton omsettes med hverandre, hvorved bis(metobromidet) av N-metyl-N-(1-metyl-3- [2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] - propyl) -3- (4-morfolinyl) -propylamin- propylamine and excess methyl bromide in acetone react with each other, whereby the bis(methobromide) of N-methyl-N-(1-methyl-3-[2,6,6-trimethyl-cyclohexene-(1)-yl-(1)] - propyl) -3-(4-morpholinyl) -propylamine-

sesquihydrat med smeltepunkt 213—225° C sesquihydrate with melting point 213-225° C

(under spaltning) fås etter utkrystallise- (under cleavage) is obtained after crystallization

ring fra 95 pst.'s etylalkohol-nitrometan- ring from 95 percent ethyl alcohol-nitromethane-

eter. ether.

Eksempel 27. Example 27.

15 g (0,042 mol) N-metyl-N-(2-metyl- 15 g (0.042 mol) N-methyl-N-(2-methyl-

4- [2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] - butyl)-3-(4-morfolinyl)-propylamin og overskytende metylbromid i aceton omset- 4-[2,6,6-trimethyl-cyclohexen-(1)-yl-(1)]-butyl)-3-(4-morpholinyl)-propylamine and excess methyl bromide in acetone reacted

tes med hverandre på den i eksempel 22 are tested with each other on the one in example 22

beskrevne måte, hvorved man får bis(me- described way, whereby one gets bis(me-

tobromidet) av N-metyl-N-(2-metyl-4-[2,6,6-trimetyl-cykloheksen- (1) -yl- (1) ] - butyl) -3- (4-morfolinyl) -propylamin med smeltepunkt 206—208° C (under spaltning) the tobromide) of N-methyl-N-(2-methyl-4-[2,6,6-trimethyl-cyclohexen-(1)-yl-(1)]-butyl)-3-(4-morpholinyl)-propylamine with melting point 206—208° C (under decomposition)

etter omkrystallisering fra nitrometan- after recrystallization from nitromethane-

eter. ether.

Eksempel 28. Example 28.

10 g (0,027 mol) ^.NT-dietyl-N-metyl-N2-(2-metyl-4-[2,6,6-trimetyl-cykloheksen-(1) -yl- (1) ] -butyl) -1,4-pentylen-diamin lø- 10 g (0.027 mol) ^.NT-diethyl-N-methyl-N2-(2-methyl-4-[2,6,6-trimethyl-cyclohexene-(1)-yl-(1)]-butyl)- 1,4-pentylene-diamine solution

ses i 100 cm<3> aceton, og denne oppløsning tilsettes 14 g (0,14 mol) metyljodid. Denne oppløsning las henstå i 3 dager ved væ- is seen in 100 cm<3> of acetone, and 14 g (0.14 mol) of methyl iodide is added to this solution. This solution is allowed to stand for 3 days by wet-

relsestemperatur og deretter konsentreres til et lite volum, hvorpå den erholdte olje krystalliseres fra etylalkohol. Derved fås bis(metojodidet) av N<1>,N<1->dietyl-N<2->metyl-N2-(2-metyl-4-[2,6,6-trimetylcykloheksen-(1) -yl- (1) ] -butyl) -1,4-pentylen-diamin med smeltepunkt 138—140° C. room temperature and then concentrated to a small volume, whereupon the oil obtained is crystallized from ethyl alcohol. This gives the bis(methiodide) of N<1>,N<1->diethyl-N<2->methyl-N2-(2-methyl-4-[2,6,6-trimethylcyclohexene-(1)-yl- (1) ]-butyl)-1,4-pentylene-diamine with a melting point of 138-140° C.

CH;>, CH:; CH;>, CH:;

- CH, - CH, - CH - (CH,)„ - N - alkylen - R, \/\ " " 1 " 1 - CH, - CH, - CH - (CH,)„ - N - alkylene - R, \/\ " " 1 " 1

CH CH.., R CH CH.., R

i hvilken n betyr tallet 0 eller 1, in which n means the number 0 or 1,

R vannstoff eller en alkyl- eller acyl- R hydrogen or an alkyl or acyl

Claims

1. Process for the production of therapeutically active amines with the general formula group and Ri a dialkylamino-, piperidine-, morpholine or pyrrolidine residue and salts thereof, characterized in that (3-ionone or 4-[2,6,6-trimethyl-cyclohexen-(1)-yl]-2-methylbutene-(2 )-al-(l) is reacted with a diamine of the general formula HjN-(alkylene)-Ri in which Rt means a dialkylamino, piperidine, morpholine or pyrrolidine residue, in the presence of a reducing agent, preferably catalytically activated hydrogen, whereupon, if desired, the amine obtained is acylated or alkylated in a known manner and/or converted into a normal or quaternary salt.

2. Method according to claim 1, characterized in that 4-[2,6,6-trimethyl-cyclohexen-(1)-yl]-2-methylbuten-(2)-al-(1) is reacted with 3-dimethylaminopropylamine in the presence of catalytically activated hydrogen and treats the thus obtained N'-(2-methyl-4-[2,6,6-trimethyl-cyclohexen-(1)-yl-(1)]-butyl)-N-,N2-dimethyl -1,3-propyleneamine with a mixture of formic acid and formaldehyde, whereupon the resulting N-methylated product is transferred by means of methyl bromide into the bis(methobromide) of N<1->(2-methyl-4-[2,6,6-trimethyl-cyclohexene-(1)-yl-(1)]-butyl)-N ',N-,N<J->trimethyl-1,3-propylene-diamine.

3. Process according to claim 1, characterized in that [3-ionone is reacted with 3-dimethylaminopropylamine in the presence of catalytically activated hydrogen and treats the thus obtained N<1->(1-methyl-3-[2,6,6-trimethyl -cyclohexene-(1)-yl-(1)]-propyl)-N-',N<2->dimethyl-1,3-propylenediamine with a mixture of formic acid and formaldehyde, after which the obtained N-methylated product is transferred by means of methyl bromide in the bis(methobromide) of NMl-methyl-3-[2,6,6-trimethyl-cyclohexen-(1)-yl-(1)]-propyl)-N<1>,N-,N --trimethyl-1,3-propylene-diamine.