NO124268B

NO124268B -

Info

Publication number: NO124268B
Application number: NO36469A
Authority: NO
Inventors: G Heitmann
Original assignee: Metallgesellschaft Ag
Priority date: 1968-02-08
Filing date: 1969-01-30
Publication date: 1972-03-27
Also published as: AT291319B; FR2001568A1; ES363307A1; GB1203532A; BE728153A; JPS514929B1; PL76027B1; SE356313B

Description

Fremgangsmåte til fremstilling av derivater av 4-oksykumarin. Process for the production of derivatives of 4-oxycoumarin.

Det er kjent en fremgangsmåte til fremstilling av derivater av 4-oksykumarin, A method is known for the production of derivatives of 4-oxycoumarin,

som består deri at 4-oksykumarin eller dettes i bensolkjernen substituerte derivater kondenseres med benzhydrol eller dettes kjernesubstituerte produkter. which consists in that 4-oxycoumarin or its derivatives substituted in the benzene ring are condensed with benzhydrol or its ring-substituted products.

Ved videre undersøkelse ble det funnet at 4-oksykumarin og dettes i bensolkjernen substituerte produkter kan kondenseres også med aryl-alkyl-karbinoler. Upon further investigation, it was found that 4-oxycoumarin and its products substituted in the benzene nucleus can also be condensed with aryl-alkyl-carbinols.

Blant de aryl-alkyl-karbinoler som kan anvendes i den nye fremgangsmåte kan det som eksempel nevnes følgende: fenyl-metyl karbinoL fenyl-etyl-karbinol, fenyl-propyl-karbinol, fenyl-isopropyl-karbinol, fenyl-butyl-karbinol, fenyl-tert.-butyl-karbinol, fenyl-pentyl-karbinol, fenyl-cykloheksyl-karbinol, 4-klorfenyl-etyl-karbinol, 4-metoksy-fenyl-metyl-karbinol, 4-metoksy-fenyl-etyl-karbinol, 4-metyl-fenyl-etyl-karbinol, 3-klorfenyl-etyl-karbinol, 4-etoksy-fenyl-etyl-karbinol, 2-klorfenyl-etylkarbinol, a-naftyl-metyl-karbinol, fenyl Among the aryl-alkyl-carbinols that can be used in the new process, the following can be mentioned as examples: phenyl-methyl carbinol, phenyl-ethyl-carbinol, phenyl-propyl-carbinol, phenyl-isopropyl-carbinol, phenyl-butyl-carbinol, phenyl -tert.-butyl-carbinol, phenyl-pentyl-carbinol, phenyl-cyclohexyl-carbinol, 4-chlorophenyl-ethyl-carbinol, 4-methoxy-phenyl-methyl-carbinol, 4-methoxy-phenyl-ethyl-carbinol, 4- methyl-phenyl-ethyl-carbinol, 3-chlorophenyl-ethyl-carbinol, 4-ethoxy-phenyl-ethyl-carbinol, 2-chlorophenyl-ethyl-carbinol, a-naphthyl-methyl-carbinol, phenyl

-bensyl-karbinol. Aryl-alkyl-karbinolene -benzyl carbinol. The aryl alkyl carbinols

kan fremstilles på kjent måte, f. eks. ved reduksjon av de tilsvarende aryl-alkylke-toner, ved forsåpning av tilsvarende a-aryl-a-halogenalkaner^ eller ved gridnard-syntese. can be produced in a known manner, e.g. by reduction of the corresponding aryl-alkyl ketones, by saponification of corresponding α-aryl-α-haloalkanes^ or by gridnard synthesis.

Videre ble det funnet, at 4-oksykumarin Furthermore, it was found that 4-oxycoumarin

og dettes i bensolkjernen substituerte derivater også kan kondenseres med slike aryl-alkyl-karbinoler hvis alkyl-rest er karbocyklisk eller heterosyklisk tilknyttet arylresten. and these derivatives substituted in the benzene ring can also be condensed with such aryl-alkyl-carbinols whose alkyl residue is carbocyclically or heterocyclically linked to the aryl residue.

Blant cykliske aryl-alkyl-karbinoler som kan anvendes er f. eks. al.-a-tetralol, a-indanol, 4-oksykroman, 3-oksy-kumaran, Among cyclic aryl-alkyl-carbinols that can be used are e.g. al.-α-tetralol, α-indanol, 4-oxycromane, 3-oxy-coumarane,

4-oksy-N-metyl-tetrahydrochinolin, ace-naftol, 1,4-dioksy-tetrahydronaftalin, 1,5-dioksy-tetrahydronaftalin. 4-oxy-N-methyl-tetrahydroquinoline, ace-naphthol, 1,4-dioxy-tetrahydronaphthalene, 1,5-dioxy-tetrahydronaphthalene.

Blant kumarinderivatene kan det som eksempel nevnes følgende: 6- og 7-klor-4-oksy-kumarin, 6- og 7-metyl-4-oksy-kumarin, 6- og 7-metoksy-4-oksy-kumarin, 7,8-benso-4-oksy-kumarin og 5,6-benso-4-oksy-kumarin. Disse kumarinderivater kan fremstilles på kjent vis> f. eks. ved kondensering av passende o-oksy-aryl-metyl-ketoner med kullsyreestere, under innvirkning av natrium, natriumalkoholat eller natriumhydrid. Among the coumarin derivatives, the following can be mentioned as an example: 6- and 7-chloro-4-oxy-coumarin, 6- and 7-methyl-4-oxy-coumarin, 6- and 7-methoxy-4-oxy-coumarin, 7, 8-benzo-4-oxy-coumarin and 5,6-benzo-4-oxy-coumarin. These coumarin derivatives can be prepared in a known manner> e.g. by condensation of suitable o-oxy-aryl-methyl-ketones with carbonic acid esters, under the action of sodium, sodium alcoholate or sodium hydride.

Endelig ble det også funnet, at det til kondensering med 4-oksy-kumarin og dettes substitusjonsprodukter også kan anvendes slike derivater av diaryl-karbinoler eller arylalkylkarbinoler, som i stedet for hydrooksylgruppen inneholder en alkyl-etergruppe, en acyloksygruppe eller et halogenatom, fortrinsvis et klor- eller brom-atom. Finally, it was also found that such derivatives of diaryl carbinols or arylalkyl carbinols can also be used for condensation with 4-oxycoumarin and its substitution products, which instead of the hydroxyl group contain an alkyl ether group, an acyloxy group or a halogen atom, preferably a chlorine or bromine atom.

De nevnte forbindelser svarer til den alminnelige formel The aforementioned compounds correspond to the general formula

hvor R1 er en arylrest, R2 er en aryl- eller alkylrest, og hvor resten R2 — hvis den er en alkylrest — også kan være alicyklisk eller heterocyklisk forbundet méd arylresten R,, og hvor X betegner en alkyleter — eller en acyloksygruppe eller et halogenatom. where R1 is an aryl residue, R2 is an aryl or alkyl residue, and where the residue R2 — if it is an alkyl residue — can also be alicyclically or heterocyclically connected with the aryl residue R,, and where X denotes an alkyl ether — or an acyloxy group or a halogen atom .

Som eksempel på slike karbinolderi-vater kan det nevnes: Bens-hydryl-metyl- i eter, benshydryl-etyleter, benshydryl-bensyl-eter, benshydrylacetat, benshydryl-. bensoat, benshydrylklorid, benshydrylbro-mid, 44'-diklor-benshydryl, metyleter, 4,4'-diklorbenshydrylacetat: ct-metoksy-etyl-bensol, a-etoksy-etylbensol, a-bensyloksy-etylbensol, a-acetoksy-etylbensol, a-klor-etyl-bensol, a-brometylbensol, fenyl-metyl-karbinol-O-bensolsulfonsyreester, a-metoksy-4-kloretylbensol, a-metoksy-4-metyl-etylbensol, a-metoksy-n-propylbensol, a-acetoksy-n-propylbensol, a-metoksy-4-metyl-n-propylbensol, a-brom-n-propylbensol, a-metoksy-n-butylbensol; al.-a-tetralol-metyleter, al.-u-acetoksy-tetralin, al.-a-brom-tetralin; a-oksy-hydrinden-metyleter, a-acet-oksy-hydrinden, a-klor-hydrinden; y-acetoksy-kroman, y-kromanolmetyleter. Examples of such carbinol derivatives can be mentioned: Benzhydryl methyl ether, benzhydryl ethyl ether, benzhydryl benzyl ether, benzhydryl acetate, benzhydryl. benzoate, benzhydryl chloride, benzhydryl bromide, 44'-dichloro-benzhydryl, methyl ether, 4,4'-dichlorobenzhydryl acetate: ct-methoxy-ethyl-benzene, a-ethoxy-ethyl-benzene, a-benzyloxy-ethyl-benzene, a-acetoxy-ethyl-benzene, a-chloro-ethyl-benzene, a-bromomethylbenzene, phenyl-methyl-carbinol-O-benzenesulfonic acid ester, a-methoxy-4-chloroethylbenzene, a-methoxy-4-methyl-ethylbenzene, a-methoxy-n-propylbenzene, a- acetoxy-n-propylbenzene, α-methoxy-4-methyl-n-propylbenzene, α-bromo-n-propylbenzene, α-methoxy-n-butylbenzene; al.-α-tetralol methyl ether, al.-u-acetoxy-tetralin, al.-α-bromo-tetralin; α-oxyhydrindene methyl ether, α-acetoxyhydrindene, α-chlorohydrindene; y-acetoxy-chroman, y-chromanol methyl ether.

Kondensasjonen ,av 4-oksykumarinene med aryl-alkyl-karbinolene kan skje ved oppvarmning i oppløsningsmidler som iseddik, med eller uten tilsetning av kon-denseringsmidler som f. eks. svovelsyre, sinkklorid, amidosulfonsyre, toluolsulion-syre, fosforsyre, borfluorid, klorvannstoff, aluminiumklorid, eller også ved oppløsning i svovelsyre av høyere konsentrasjon. Kon-denseringen kan også skje ved at komponentene opphetes i smeltet tilstand, med eller uten tilsetning av kondensasjons-midler. The condensation of the 4-oxycoumarins with the aryl-alkyl carbinols can take place by heating in solvents such as glacial acetic acid, with or without the addition of condensing agents such as e.g. sulfuric acid, zinc chloride, amidosulphonic acid, toluene sulionic acid, phosphoric acid, boron fluoride, hydrogen chloride, aluminum chloride, or also by dissolving in sulfuric acid of a higher concentration. Condensation can also take place by heating the components in a molten state, with or without the addition of condensation agents.

De produkter som fås ved fremgangs-måten er delvis kjent fra før. De har en sterk hemmende innvirkning på koaguler - ing av blod. og de kan også anvendes til å bekjempe skadelige vesener. The products obtained by the method are partially known from before. They have a strong inhibitory effect on blood coagulation. and they can also be used to fight harmful beings.

I forhold til de kjente fremgangsmåter til fremstilling av denne art av forbindelser har den nye fremgangsmåte den fordel at man kan arbeide i ett trinn og at anven-delsesområdet er bredere. In relation to the known methods for producing this type of compounds, the new method has the advantage that one can work in one step and that the area of application is wider.

Eksempel 1. Example 1.

8 vektsdeler 4-oksykumarin og 9 vektsdeler metylfenylkarbinol oppløses i varmen i 30 volumdeler iseddik. hvoretter det tildryppes 2 volumdeler konsentrert svovelsyre og det hele opphetes i 2 timer under anvendelse av tilbakeløpskjøling. Deretter blir reaksjonsblandingen helt ut på is, re-aksjohsproduktet blir filtrert fra, tatt opp i eter, og eteroppløsningen blir ekstrahert med fortynnet natronlut. Den vandige ekstrakt syres med fortynnet saltsyre, og det utfelte reaksjonsprodukt filtreres fra og tørkes. Ved omkrystallisering fra bensol får 8 parts by weight of 4-oxycoumarin and 9 parts by weight of methylphenylcarbinol are dissolved in the heat in 30 parts by volume of glacial acetic acid. after which 2 parts by volume of concentrated sulfuric acid are added dropwise and the whole is heated for 2 hours using reflux cooling. The reaction mixture is then poured onto ice, the reaction product is filtered off, taken up in ether, and the ether solution is extracted with dilute caustic soda. The aqueous extract is acidified with dilute hydrochloric acid, and the precipitated reaction product is filtered off and dried. By recrystallization from benzol sheep

man 3- (a-f enyletyl)-4-oksy-kumarin, som smelter ved 208—209°. man 3-(α-phenylethyl)-4-oxy-coumarin, which melts at 208-209°.

Eksempel 2. Example 2.

Man oppløser i varmen 8 vektsdeler 6-klor-4-oksy-kumarin og 9 vektsdeler metyl-fenyl-karbinol i .50 volumdeler iseddik, In the heat, 8 parts by weight of 6-chloro-4-oxy-coumarin and 9 parts by weight of methyl-phenyl-carbinol are dissolved in .50 parts by volume of glacial acetic acid,

drypper til 3 volumdeler konsentrert svovelsyre, og oppheter 2 timer med tilbakeløps-kjøling. Opparbeidelsen skjer som angitt i eksempel 1. Det erholdte 6-klor-3-[a-f enyletyl]-4-oksy-kumarin omkrystalliseres fra 80 pst.'s eddiksyre. Smpkt. 208— 211° C. drip to 3 parts by volume concentrated sulfuric acid, and heat for 2 hours with reflux cooling. The processing takes place as indicated in example 1. The 6-chloro-3-[α-phenylethyl]-4-oxycoumarin obtained is recrystallized from 80 percent acetic acid. Smpct. 208— 211° C.

Eksempel 3. Example 3.

100 vektsdeler 4-oksy-kumarin utrøres ved 100° C i 100 volumdeler iseddik og 30 volumdeler svovelsyre (60° Bé). Deretter drypper man til 100 vektsdeler fenyletyl-karbinol. Deretter omrører man 1 time ved 100—110° C, heller blandingen ut på is og tar reaksjonsproduktet opp i toluol. Toluol-laget ekstraheres fullstendig med fortynnet natronlut, og det vandige lag filtreres under tilsetning av aktivt kull, og syres koldt med fortynnet saltsyre. Det utfelte reaksjonsprodukt filtreres fra,wvaskes med vann og tørkes. Utbyttet er 125 vektsdeler 3-(a-f enyl-propyl)-4-oksykumarin, med smeltepunkt 178—179° C omkrystallisert fra fortynnet alkohol. 100 parts by weight of 4-oxy-coumarin are stirred at 100° C in 100 parts by volume of glacial acetic acid and 30 parts by volume of sulfuric acid (60° Bé). 100 parts by weight of phenylethyl carbinol are then added. The mixture is then stirred for 1 hour at 100-110° C, the mixture is poured onto ice and the reaction product is taken up in toluene. The toluene layer is extracted completely with dilute caustic soda, and the aqueous layer is filtered while adding activated carbon, and acidified cold with dilute hydrochloric acid. The precipitated reaction product is filtered off, washed with water and dried. The yield is 125 parts by weight of 3-(α-phenyl-propyl)-4-oxycoumarin, with a melting point of 178-179° C recrystallized from dilute alcohol.

Eksempel 4. Example 4.

8 vektsdeler 4-oksykumarin og 10 vektsdeler 4-klorfenyl-metyl-karbinol oppløses varmt i 40 volumdeler iseddik, og det dryppes til 3 volumdeler konsentrert svovelsyre. Deretter oppheter, man i iy2 time med til-bakeløpskjøling, og opparbeider videre som i eksempel 1. Det erholdte 3-(<x-4'-klorfenyl -etyl)-4-oksykumarin omkrystalliseres fra fortynnet alkohol. Smpkt. 183—185° C. 8 parts by weight of 4-oxycoumarin and 10 parts by weight of 4-chlorophenyl-methyl-carbinol are dissolved hot in 40 parts by volume of glacial acetic acid, and it is dripped into 3 parts by volume of concentrated sulfuric acid. It is then heated for 1y2 hours with reflux cooling, and further worked up as in example 1. The obtained 3-(<x-4'-chlorophenyl-ethyl)-4-oxycoumarin is recrystallized from dilute alcohol. Smpct. 183-185° C.

Eksempel 5. Example 5.

8 vektsdeler 4-oksy-kumarin og 10 8 parts by weight of 4-oxy-coumarin and 10

• vektsdeler 4-metoksy-fenyl-etyl-karbinol • smeltes homogent ved 100° C og det tildryppes langsomt 1.0 volumdeler 50 pst.'s svovelsyre. Blandingen holdes derpå i 1 t time ved 100—110°, og opparbeides deretter - på den i eksempel 1 angitte måte. Man t får 3-(a-4'-metoksy-fenyl-propyl) -4-oksy-; kumarin. Smeltepunkt 141—143°, krystal-r lisert fra vaskebensin. • parts by weight of 4-methoxy-phenyl-ethyl-carbinol • melt homogeneously at 100° C and slowly add 1.0 parts by volume of 50 percent sulfuric acid. The mixture is then held for 1 hour at 100-110°, and then worked up - in the manner indicated in example 1. Man t obtains 3-(α-4'-methoxy-phenyl-propyl)-4-oxy-; coumarin. Melting point 141-143°, crystallized from benzine.

Eksempel 6: Example 6:

8 vektsdeler 4-oksykumarin og 10 vektsdeler 4-klorfenyl-metyl-karbinol smeltes homogent ved 130° C under tilsetning av 3 volumdeler iseddik' og det tildryppes langsomt 0,5 volumdeler svovelsyre (av 60° Bé). Temperaturen holdes deretter 1 time ved 130° C, og man opparbeider på den i eksempel 1 angitte måte. Det fås 3-(a-4'-klorf enyl-etyl) -4-oksy-kumarin. Utbyttet er 10 vektsdeler. 8 parts by weight of 4-oxycoumarin and 10 parts by weight of 4-chlorophenyl-methyl-carbinol are melted homogeneously at 130° C with the addition of 3 parts by volume of glacial acetic acid and slowly 0.5 parts by volume of sulfuric acid (of 60° Bé) are added dropwise. The temperature is then maintained for 1 hour at 130° C, and work-up is carried out in the manner indicated in example 1. 3-(α-4'-chlorophenylethyl)-4-oxycoumarin is obtained. The yield is 10 parts by weight.

Eksempel 7. Example 7.

8 vektsdeler 4-oksy-kumarin og 10 vektsdeler fenyl-etyl-karbinol smeltes homogent ved 160—170°, og det tildryppes langsomt 1 volumdel 30 pst.'s svovelsyre. Deretter holdes temperaturen på 160° i 15 minutter, og man opparbeider på den i eksempel 1 angitte måte. Det fås 3-(a-fenylpropyl)-4-oksykumarin, som har smeltepunkt 178—179° C. 8 parts by weight of 4-oxycoumarin and 10 parts by weight of phenyl-ethyl-carbinol are melted homogeneously at 160-170°, and 1 part by volume of 30 per cent sulfuric acid is slowly added dropwise. The temperature is then kept at 160° for 15 minutes, and it is worked up in the manner indicated in example 1. 3-(a-phenylpropyl)-4-oxycoumarin is obtained, which has a melting point of 178-179° C.

Eksempel 8. Example 8.

8 vektsdeler 7-metyl-4-oksy-kumarin cg 9 vektsdeler fenyl-etyl-karbinol opphetes til ca. 100° C under tilsetning av 5 volumdeler iseddik, hvoretter det langsomt tildryppes 1 volumdel svovelsyre av 60° Bé. Deretter opphetes blandingen 1 time ved 120° C, helles i vann, og opparbeides som angitt i eksempel 1. Man får 7-metyl-3-(a-f enyl-propyl) -4-oksykumarin. (Smeltepunkt 160—162° C etter omkrystallisering fra fortynnet metanol). 8 parts by weight of 7-methyl-4-oxy-coumarin and 9 parts by weight of phenyl-ethyl-carbinol are heated to approx. 100° C while adding 5 parts by volume of glacial acetic acid, after which 1 part by volume of sulfuric acid of 60° Bé is slowly added dropwise. The mixture is then heated for 1 hour at 120° C, poured into water, and worked up as indicated in example 1. 7-methyl-3-(α-phenyl-propyl)-4-oxycoumarin is obtained. (Melting point 160-162° C after recrystallization from dilute methanol).

Hvis det ovenfor nevnte kumarin-derivat erstattes med den samme mengde 7-klor-4-oksy-kumarin får man 7-klor-3-(a-f enyl-propyl) -4-oksy-kumarin, som smelter ved 165°—166° etter omkrystallisering fra fortynnet metanol. If the above-mentioned coumarin derivative is replaced by the same amount of 7-chloro-4-oxy-coumarin, 7-chloro-3-(α-phenyl-propyl)-4-oxy-coumarin is obtained, which melts at 165°—166° after recrystallization from dilute methanol.

Eksempel 9. Example 9.

8 vektsdeler 4-oksy-kumarin og 10 vektsdeler p-tolyl-etyl-karbinol opphetes ved 100° C sammen med 5 volumdeler iseddik, og det tildryppes langsomt 1 volumdel svovelsyre av 60° Bé. Deretter oppheter man 1 time ved 120°, heller reaksjonsblandingen ut i vann, og opparbeider som van-lig over natriumsaltet. Man får 3-(a-p-tolyl-propyl) -4-oksy-kumarin, som omkrystallisert fra fortynnet metanol smelter ved 131—132° C. 8 parts by weight of 4-oxy-coumarin and 10 parts by weight of p-tolyl-ethyl-carbinol are heated at 100° C together with 5 parts by volume of glacial acetic acid, and 1 part by volume of sulfuric acid of 60° Bé is slowly added dropwise. Then heat for 1 hour at 120°, pour the reaction mixture into water, and work up as usual over the sodium salt. 3-(a-p-tolyl-propyl)-4-oxy-coumarin is obtained, which melts at 131-132° C when recrystallized from dilute methanol.

Hvis 4-oksy-kumarinet erstattes med den samme mengde 7-metyl-4-oksy-kumarin If the 4-oxy-coumarin is replaced by the same amount of 7-methyl-4-oxy-coumarin

får man 7-metyl-3-(a-p-tolyl-propyl) 4-oksy-kumarin (smeltepunkt 151—153° C). 7-methyl-3-(a-p-tolyl-propyl) 4-oxycoumarin (melting point 151-153° C) is obtained.

Erstatter man p-tolyletyl-karbinolen med p-klorfenyl-etyl-karbinol får man 3-(a-p-klorf enyl-propyl)-4-oksy-kumarin (smeltepunkt 192—192,5° C. If you replace the p-tolylethyl carbinol with p-chlorophenyl-ethyl-carbinol, you get 3-(a-p-chlorophenyl-propyl)-4-oxy-coumarin (melting point 192-192.5° C.

Eksempel 10. Example 10.

8 vektsdeler 4-oksy-kumarin og 11 vektsdeler fenyl-butyl-karbinol opphetes sammen med 7 volumdeler iseddik til 100° C, og det tildryppes 1 volumdel svovelsyre av 60° Bé, hvorved alt går i oppløsning. Reaksjonsblandingen holdes en time på 110— 120° og helles deretter i vann, og opparbeides over natriumsaltet. Fra fortynnet alkohol krystalliserer det ut 3-(a-fenyl-n-pentyl-)-4-oksy-kumarin (smeltepunkt 183 —184°). 8 parts by weight of 4-oxy-coumarin and 11 parts by weight of phenyl-butyl-carbinol are heated together with 7 parts by volume of glacial acetic acid to 100° C, and 1 part by volume of sulfuric acid of 60° Bé is added dropwise, whereby everything dissolves. The reaction mixture is kept for one hour at 110-120° and is then poured into water and worked up over the sodium salt. 3-(a-phenyl-n-pentyl-)-4-oxy-coumarin (melting point 183-184°) crystallizes from diluted alcohol.

På analog måte får man av 4-oksykumarin og fenylcykloheksyl-karbinol stoffet 3- (f enyl-cykloheksyl-metyl) -4-oksy-kumarin, som omkrystallisert fra fortynnet alkohol smelter ved 207—208° C, og med fenylisopropyl-karbinol fås det 3-(a-fenyl^In an analogous way, from 4-oxycoumarin and phenylcyclohexyl-carbinol, the substance 3-(phenyl-cyclohexyl-methyl)-4-oxy-coumarin is obtained, which, recrystallized from dilute alcohol, melts at 207-208° C, and with phenylisopropyl-carbinol is obtained the 3-(a-phenyl^

(3-metyl-propyl)-4-oksykumarin, som etter omkrystallisering fra fortynnet alkohol smelter ved 204—205° C. (3-methyl-propyl)-4-oxycoumarin, which after recrystallization from dilute alcohol melts at 204-205° C.

Eksempel 11. Example 11.

Man suspenderer 250 vektsdeler 4-oksy-kumarin i 200 volumdeler iseddik og 30 volumdeler svovelsyre (60° Bé) og oppheter til 110° C under omrøring. Deretter ble det i løpet av 30 minutter tildryppet 275 vektsdeler p-tolyletyl-karbinol, hvoretter det omrøres i 30 min. ved den samme temperatur. Deretter blir reaksjonsblandingen heilt ut i vann, det halvfaste reaksjonsprodukt blir tatt opp i toluol, og toluoloppløsningen ekstraheres med 4 pst.'s natronlut. Den vandige ekstrakt filtreres gjennom aktive kull og syres. Etter filtre-ring og tørking får man 340 vektsdeler 3-[a- (p-tolyl) -propyl] -4-oksykumarin, som smelter ved 140—141° etter omkrystallisering fra fortynnet alkohol. 250 parts by weight of 4-oxycoumarin are suspended in 200 parts by volume of glacial acetic acid and 30 parts by volume of sulfuric acid (60° Bé) and heated to 110° C with stirring. 275 parts by weight of p-tolylethyl carbinol were then added dropwise over the course of 30 minutes, after which it was stirred for 30 minutes. at the same temperature. The reaction mixture is then poured into water, the semi-solid reaction product is taken up in toluene, and the toluene solution is extracted with 4% caustic soda. The aqueous extract is filtered through activated charcoal and acidified. After filtering and drying, 340 parts by weight of 3-[a-(p-tolyl)-propyl]-4-oxycoumarin are obtained, which melts at 140-141° after recrystallization from dilute alcohol.

På analog måte får man ved anvendelse av 4-oksykumarin følgende forbindelser. In an analogous way, the following compounds are obtained by using 4-oxycoumarin.

Med fenyl-n-propyl-karbinol fås 3-[a-f enyl-n-butyl] -4-oksykumarin (smeltepunkt 200—201° C), med p-tolyl-n-propyl-karbinol fås 3-[a-(p-tolyl)-n-butyl]-4-oksy-kumarin (smeltepunkt 137—138°)' med p-anisyl-propyl-karbinol fås 3-[a-(p-anisyl) -n-butyl] -4-oksy-kumarin, With phenyl-n-propyl-carbinol you get 3-[a-phenyl-n-butyl]-4-oxycoumarin (melting point 200-201° C), with p-tolyl-n-propyl-carbinol you get 3-[a-(p -tolyl)-n-butyl]-4-oxy-coumarin (melting point 137-138°)' with p-anisyl-propyl-carbinol gives 3-[a-(p-anisyl)-n-butyl]-4-oxy -coumarin,

med p-tolyl-n-butyl-karbinol fås 3-[a-(p- with p-tolyl-n-butyl-carbinol gives 3-[a-(p-

tolyl) -n-pentyl] -4-oksy-kumarin (smeltepunkt 160—162°), med p-isopropyl-fenyl-metyl-karbinol fås 3-[a(p-isopropyl-fenyl/ etyl]-4-oksy-kumarin (smeltepunkt 158— 160°), med p-isopropyl-fenyl-etyl-karbinol fås 3-[tx(p-isopropyl-fenyl)-n-propyl]-4-oksy-kumarin (smeltepunkt 144—146°), med p-etyl-fenyi-metyl-karbinol fås 3-[a-(p-etyl-f enyl) -etyl] -4-oksy-kumarin (smeltepunkt 158—160°), tolyl)-n-pentyl]-4-oxy-coumarin (melting point 160—162°), with p-isopropyl-phenyl-methyl-carbinol 3-[a(p-isopropyl-phenyl/ethyl]-4-oxy- coumarin (melting point 158—160°), with p-isopropyl-phenyl-ethyl-carbinol gives 3-[tx(p-isopropyl-phenyl)-n-propyl]-4-oxy-coumarin (melting point 144—146°), with p-ethyl-phenyl-methyl-carbinol gives 3-[a-(p-ethyl-phenyl)-ethyl]-4-oxy-coumarin (melting point 158-160°),

med p-etylfenyl-etyl-karbinol fås 3-[a-(p-etyl-f enyl) -n-propyl] -4-oksy-kamarin smeltepunkt 134—137°), med 3,4-dimetyl-fenyl-metyl-karbinol fås 3-[a-(3',4'-dimetyl -fenyl) -etyl] -4-oksy-kumarin (smltpkt. 178—179°), med 34-dimetyl-fenyl-etyl-karbinol fås 3-[a-(3',4'-dimetyl-fenyl-n-propyl]-4-oksy-kumarin (smeltepunkt 184 —185°), with p-ethylphenyl-ethyl-carbinol gives 3-[a-(p-ethyl-phenyl)-n-propyl]-4-oxy-camarin melting point 134-137°), with 3,4-dimethyl-phenyl-methyl -carbinol gives 3-[a-(3',4'-dimethyl-phenyl)-ethyl]-4-oxy-coumarin (m.p. 178—179°), with 34-dimethyl-phenyl-ethyl-carbinol gives 3- [α-(3',4'-dimethyl-phenyl-n-propyl]-4-oxy-coumarin (melting point 184 -185°),

med p-fluorfenyl-metyl-karbinol fås 3-[ct-f luorf enyl) -etyl-4-oksy-kumarin (smeltepunkt 182—184°), with p-fluorophenyl-methyl-carbinol 3-[ct-fluorophenyl)-ethyl-4-oxy-coumarin is obtained (melting point 182-184°),

med p-fluorfenyl-etylkabinol fås 3-[a-(p-f luorf enyl) -n-propyl] -4-oksy-kumarin (smeltepunkt 175—177°), with p-fluorophenyl-ethylcabinol 3-[a-(p-fluorophenyl)-n-propyl]-4-oxy-coumarin is obtained (melting point 175-177°),

med p-difenylyl-metyl-karbinol fås 3-[a-(p-difenylyl) -etyl] -4-oksy-kumarin (smeltepunkt 192—193°). with p-diphenylyl-methyl-carbinol gives 3-[a-(p-diphenylyl)-ethyl]-4-oxy-coumarin (melting point 192-193°).

Av l,4-bis-(a-oksyetyl)-bensol (erholdt ved katalyttisk hydrering av 1,4-diacetyl-bensol) og 4-oksykumarin får man ved analog arbeidsmåte et polymert kondensa-sjonsprodukt, som også har antikoaguler-ende egenskaper. From 1,4-bis-(a-oxyethyl)-benzene (obtained by catalytic hydrogenation of 1,4-diacetyl-benzene) and 4-oxycoumarin, a polymeric condensation product is obtained by an analogous procedure, which also has anticoagulant properties .

Hvis man anvender 7-metyl-4-oksykumarin som utgangsmateriale får man føl-gende forbindelser: med fenyl-metyl-karbinol fås 7-metyl -3-(a-fenyl-etyl) -4-oksy-kumarin (smeltepunkt 185—186°), If 7-methyl-4-oxycoumarin is used as starting material, the following compounds are obtained: with phenyl-methyl-carbinol, 7-methyl-3-(a-phenyl-ethyl)-4-oxy-coumarin is obtained (melting point 185-186 °),

med p-etylfenyl-etyl-karbinol fås 7-metyl-3- [a- (p-etyl-f enyl) -n-propyl] -4-oksy-kumarin (smeltepunkt 169—171°), with p-ethylphenyl-ethyl-carbinol 7-methyl-3-[a-(p-ethyl-phenyl)-n-propyl]-4-oxy-coumarin is obtained (melting point 169-171°),

med p-anisyl-etyl-karbinol fås 7-metyl-3-[a- (p-anisyl) -n-propyl] -4-oksy-kumarin. with p-anisyl-ethyl-carbinol 7-methyl-3-[a-(p-anisyl)-n-propyl]-4-oxy-coumarin is obtained.

Hvis man går ut fra 4-oksykumarin som utgangsmateriale får man følgende forbindelser: med 3,4-tetrametylen-fenyl-metyl-karbinol fås 3-[a-(3',4'-tetra-metylen-fenyl) etyl]-4- oksy-kumarin (smeltepunkt 137—138°), hied 3,4-tetrametylen-fenyl-etyl-karbinol fås 3- [a-3',4'-tetra-metylen-fenyl) -propyl] -4-oksy-kumarin (smeltepunkt 173-175°), med 3,4-trimetylen-fenyl-metyl-karbinol fås 3-[a-(3',4'-trimetylen-fenyl)-etyl]-4-oksy-kumarin (smeltepunkt 176°), med 3,4-trimetylen-fenyl-etyl-karbinol fås 3- [a- (3',4'-trimetylen-f enyl) -propyl] - 4- oksy-kumarin (smltp. 160—162°), med 2,5-dimetylpfenyl-metyl-karbinol fås 3- [a- (2',5'-dimetyl-f enyl) -etyl] -4-oksy-kumarin (smltpkt. 217.5—218°), med 2,5-dimetyl-fenyletyl-karbinol fås 3-[a- (2,5'-dimetyl-fenyl) -propyl] -4-oksy-kumarin (smltpkt. 215—217°), med 2,4-dimetyl-fenyl-etyl-karbinol fås 3- [a- (2',4'-dimetyl-f enyl) -propyl] -4-oksy-kumarin (smltpkt. 156—158°), med 4-fenoksy-fenyl-métyl-karbinol fås 3-[a- (4-f enoksy-f enyl) -etyl] -4-oksy-kumarin (smeltepunkt 137—138°), med 1,3-difenyl-propanol fås 3-[a, v-dif enyl-propyl) -4-oksy-kumarin (smeltepunkt 163—165°), med 3-acenaftyl-metyl-karbinol fås 3-[a-(3'-acenaf tyl) -etyl] -4-oksy-kumarin (smeltepunkt 203—205°), med p-propyl-fenyl-metyl-karbinol fås 3-[ a- (p-propyl-fenyl) -etyl] -4- oksy-kumarin (smeltepunkt 136—137°), med p-propyl-fenyl-etyl-karbinol fås 3-[a-(p-propyl-fenyl)-propyl]-4-oksy-kumarin (smeltepunkt 105—106°, med p-cykloheksyl -fenyl-metyl-karbinol fås 3-[a-(p-cykloheksyl-f enyl) -etyl] -4-oksy-kumarin (smltpkt. 170—172°, Starting from 4-oxycoumarin as starting material, the following compounds are obtained: with 3,4-tetramethylene-phenyl-methyl-carbinol, 3-[a-(3',4'-tetra-methylene-phenyl) ethyl]-4 is obtained - oxy-coumarin (melting point 137-138°), from which 3,4-tetramethylene-phenyl-ethyl-carbinol is obtained 3-[a-3',4'-tetra-methylene-phenyl)-propyl]-4-oxy- coumarin (melting point 173-175°), with 3,4-trimethylene-phenyl-methyl-carbinol gives 3-[a-(3',4'-trimethylene-phenyl)-ethyl]-4-oxy-coumarin (melting point 176°), with 3,4-trimethylene -phenyl-ethyl-carbinol is obtained 3-[α-(3',4'-trimethylene-phenyl)-propyl]-4-oxy-coumarin (m.p. 160—162°), with 2,5-dimethylpphenyl-methyl -carbinol is obtained 3-[α-(2',5'-dimethyl-phenyl)-ethyl]-4-oxy-coumarin (m.p. 217.5—218°), with 2,5-dimethyl-phenylethyl-carbinol 3-[α-(2,5'-dimethyl-phenyl)-propyl]-4-oxy-coumarin (m.p. 215-217°) is obtained, with 2,4-dimethyl-phenyl-ethyl-carbinol 3-[α-(2',4'-dimethyl-phenyl)-propyl]-4-oxy-coumarin (m.p. 156-158°) is obtained, with 4-phenoxy-phenyl-methyl-carbinol 3-[a-(4-phenoxy-phenyl)-ethyl]-4-oxy-coumarin is obtained (melting point 137-138°), with 1,3-diphenylpropanol gives 3-[a,v-diphenyl-propyl)-4-oxy-coumarin (melting point 163-165°), with 3-acenaphthyl-methyl-carbinol 3-[a-(3'-acenaphthyl)-ethyl]-4-oxy-coumarin is obtained (melting point 203-205°), with p-propyl-phenyl-methyl-carbinol 3-[a-(p-propyl-phenyl)-ethyl]-4-oxy-coumarin is obtained (melting point 136-137°), with p-propyl-phenyl-ethyl-carbinol you get 3-[a-(p-propyl-phenyl)-propyl]-4-oxy-coumarin (melting point 105-106°, with p-cyclohexyl-phenyl-methyl-carbinol you get 3-[α-(p-cyclohexyl-phenyl)-ethyl]-4-oxy-coumarin (melting point 170-172°,

med p-cykloheksyl-fenyletyl-karbinol fås 3-[ct-(p-cykloheksyl-fenyl)-propyl]-4-oksy-kumarin (smeltpkt. 178—179°). with p-cyclohexyl-phenylethyl-carbinol gives 3-[ct-(p-cyclohexyl-phenyl)-propyl]-4-oxy-coumarin (melting point 178-179°).

Eksempel 12. Example 12.

8 vektsdeler 4-oksy-kumarin og 11 vektsdeler al.-a-tetralol opphetes til 100° sammen med 5 volumdeler iseddik. Deretter drypper man langsomt til 1 volumdel svovelsyre av 60° Bé, hvorved det dannes en klar oppløsning. Reaksjonsblandingen opphetes ytterligere 1 time ved 110—120°, og helles deretter i vann, hvoretter reaksjonsproduktet tas opp i eter. Eterlaget ekstraheres med natronlut. ekstraktet filtreres over kull, og syres med fortynnet eddik - syre. Det derved utfelte reaksjonsprodukt filtreres fra og tørkes. Utbyttet blir 10 vektsdeler 3- (al.-a-tetrahydronaf tyl) -4-oksy-kumarin, som smelter ved 186—187° etter omkrystallisering fra alkohol. Denne forbindelse svarer til formelen 8 parts by weight of 4-oxy-coumarin and 11 parts by weight of al.-a-tetralol are heated to 100° together with 5 parts by volume of glacial acetic acid. Next, 1 part by volume of sulfuric acid of 60° Bé is slowly dripped in, whereby a clear solution is formed. The reaction mixture is heated for a further 1 hour at 110-120°, and then poured into water, after which the reaction product is taken up in ether. The ether layer is extracted with caustic soda. the extract is filtered over charcoal, and acidified with diluted acetic acid. The thereby precipitated reaction product is filtered off and dried. The yield is 10 parts by weight of 3-(α-tetrahydronaphthyl)-4-oxycoumarin, which melts at 186-187° after recrystallization from alcohol. This compound corresponds to the formula

På analog måte kan man av 7-klor-4-oksy-kumarin få 7-klor-3-(al.-a-tetra-hydronaftyl) -4-oksykumarin, smeltepunkt 190—191°, og av 7-metyl-4-oksy-kumarin lås 7-metyl-3-(al.-a-tetrahydronaftyl)-4-pksy-kumarin, smeltepunkt 186—187°, In an analogous way, 7-chloro-4-oxycoumarin can be obtained from 7-chloro-3-(al.-α-tetrahydronaphthyl)-4-oxycoumarin, melting point 190-191°, and from 7-methyl-4 -oxy-coumarin lock 7-methyl-3-(al.-α-tetrahydronaphthyl)-4-poxy-coumarin, melting point 186-187°,

av 6-metyl-4-oksy-kumarin fås 6-metyl-3-(al.-a-tetrahydronaf tyl)-4-oksy-kumarin, smeltepunkt 207—208,5° og av 7-metoksy-4-oksy-kumarin fås 7-metoksy-3- (al.-a-tetrahydro-naf tyl) -4-oksy-kumarin, smeltepunkt 190—192°. of 6-methyl-4-oxy-coumarin yields 6-methyl-3-(al.-a-tetrahydronaphthyl)-4-oxy-coumarin, melting point 207—208.5° and of 7-methoxy-4-oxy- coumarin is obtained 7-methoxy-3-(al.-α-tetrahydro-naphthyl)-4-oxy-coumarin, melting point 190—192°.

Eksempel 13. Example 13.

8 vektsdeler 4-oksy-kumarin og 9 vektsdeler a-indol blir etter tilsetning av 5 volumdeler iseddik oppvarmet til 70—80° C, hvoretter det langsomt dryppes til 0,5 volumdeler svovelsyre av 60° Bé. Blandingen holdes 1 time på 110—120° og opparbeides deretter på den i eksempel 1 angitte måte. Man får 3-(a-indanyl)-4-oksy-kumarin, som etter omkrystallisering fra fortynnet alkohol har smeltepunkt 196— 198°. Denne forbindelse svarer til formelen 8 parts by weight of 4-oxy-coumarin and 9 parts by weight of a-indole are, after adding 5 parts by volume of glacial acetic acid, heated to 70-80° C, after which 0.5 parts by volume of sulfuric acid of 60° Bé is slowly added in drops. The mixture is held for 1 hour at 110-120° and is then worked up in the manner indicated in example 1. 3-(α-indanyl)-4-oxy-coumarin is obtained, which after recrystallization from dilute alcohol has a melting point of 196-198°. This compound corresponds to the formula

Eksempel 14. Example 14.

8 vektsdeler 4-oksy-kumarin oppløpes i 8 parts by weight of 4-oxy-coumarin are run up in

■\ armen i 20 volumdeler iseddik og 1 volumdel svovelsyre (60° Bé) og ved ca. 100° C dryppes det til 9 vektsdeler Y-kromanol. Deretter oppheter man 30 min. ved 100— 130°, heller reaksjonsproduktet ut i vann, og tar opp i eter. Eterlaget ekstraheres med fortynnet natronlut, den vandige ekstrakt syres, og det utfelte reaksjonsprodukt filtreres fra og tørkes. Omkrystallisert fra fortynnet alkohol smelter produktet ved 210—212° C. Utbyttet er 70 % av det teore-tiske. ■\ the arm in 20 parts by volume of glacial acetic acid and 1 part by volume of sulfuric acid (60° Bé) and at approx. At 100° C, 9 parts by weight of Y-chromanol are added dropwise. Then you warm up for 30 min. at 100— 130°, pours the reaction product into water, and takes up in ether. The ether layer is extracted with dilute caustic soda, the aqueous extract is acidified, and the precipitated reaction product is filtered off and dried. Recrystallized from dilute alcohol, the product melts at 210-212° C. The yield is 70% of the theoretical.

Eksempel 15. Example 15.

8 vektsdeler 4-oksy-kumarin og 11 vektsdeler benzhydryl-metyleter smeltes homogent sammen med 5 volumdeler iseddik. hvoretter det tilsettes 1 volumdel svovelsyre av 60° Bé. Deretter oppheter man 1 time ved 120°, heller produktet ut i vann, og omkrystalliserer reaksjonsproduktet fra metanol. Det erholdte 3-benzhydryl -4-oksy-kumarin smelter ved 181—182° C. Det samme reaksjonsprodukt fås også av 4-oksy-kumarin og benzhydryl-metyl-eter -ved opphetning av smeiten til 150—160° C. I stedet for benzhydryl-metyleter kan man også anvende benzhydryletyleter, benz-hydrylacetat eller benzhydrylbromid. 8 parts by weight of 4-oxycoumarin and 11 parts by weight of benzhydryl methyl ether are homogeneously melted together with 5 parts by volume of glacial acetic acid. after which 1 part by volume of sulfuric acid of 60° Bé is added. The mixture is then heated for 1 hour at 120°, the product is poured into water, and the reaction product is recrystallized from methanol. The resulting 3-benzhydryl-4-oxy-coumarin melts at 181-182° C. The same reaction product is also obtained from 4-oxy-coumarin and benzhydryl-methyl ether -by heating the melt to 150-160° C. Instead for benzhydryl methyl ether, benzhydryl ethyl ether, benzhydryl acetate or benzhydryl bromide can also be used.

Ved analog; arbeidsmåte, får man føl-gende forbindelser: Av 7-metyl-4-oksy-kumarin fås 7-metyl-3-benzhydryl-4-oksy-kumarin (smltpkt. 184—185°), av 7-klor-4-oksy-kumarin fås 7-klor-3-benzhydryl-4-oksy-kumarin (smltpkt. 175 —176°), av 6-klor-4-oksy-kumarin fås 6-klor-3-benzhydryl-4-oksykumarin (smltpkt. 200 202°), By analog; working method, the following compounds are obtained: From 7-methyl-4-oxy-coumarin, 7-methyl-3-benzhydryl-4-oxy-coumarin is obtained (melting point 184-185°), 7-chloro-4-oxy-coumarin yields 7-chloro-3-benzhydryl-4-oxy-coumarin (melting point 175 —176°), 6-chloro-4-oxy-coumarin yields 6-chloro-3- benzhydryl-4-oxycoumarin (melting point 200 202°),

av 7-klor-4-oksy-kumarin og 4,4'-diklor-benzhydryl-metyl-eter får man 7,4',4"-tri-klor-4-oksy-kumarin (smltpkt. 213—215°), av 7-metoksy-4-oksy-kumarin og 4,4'-di-klorbenzhydrylmetyleter fås 7-metoksy-3-(4',4"-diklorbenzhydryl)-4-oksy-kumarin (smltpkt. 210—211°). of 7-chloro-4-oxy-coumarin and 4,4'-dichloro-benzhydryl-methyl ether gives 7,4',4"-tri-chloro-4-oxy-coumarin (m.p. 213-215°) , of 7-methoxy-4-oxy-coumarin and 4,4'-dichlorobenzhydryl methyl ether gives 7-methoxy-3-(4',4"-dichlorobenzhydryl)-4-oxy-coumarin (m.p. 210-211°) .

Eksempel 16. , Example 16. ,

8 deler 4-oksy-kumarin og 8 vektsdeler a-metoksy-etyl-bensol i 10 volumdeler iseddik tilsettes 1 volumdel svovelsyre av 60° Bé og holdes 1 time på 110—120° C. Deretter heller man ut i vann, tar opp reaksjonsproduktet med eter, og ekstraherer med fortynnet natronlut. Den vandige ekstrakt syres, og reaksjonsproduktet omkrystalliseres fra fortynnet alkohol. Det erholdte 3- (a-f enyl-etyl) -4-oksy-kumarin smelter ved 208—209° C. I stedet for svovelsyre kan man som kondensasjonsmiddel også anvende sinkklorid, fosforsyre eller toluolsulfosyre. Kondensasjonen kan også bevirkes ved å opphete komponentene i smeltet tilstand til over 150° C. I stedet for a-metoksy-etyl-bensol kan det også anvendes a-acetoksy-etylbensol eller a-brometylbensol. 8 parts of 4-oxy-coumarin and 8 parts by weight of a-methoxy-ethyl-benzene in 10 parts by volume of glacial acetic acid, 1 part by volume of sulfuric acid of 60° Bé is added and held for 1 hour at 110-120° C. Then you pour into water, take up the reaction product with ether, and extract with dilute caustic soda. The aqueous extract is acidified, and the reaction product is recrystallized from dilute alcohol. The 3-(α-phenylethyl)-4-oxycoumarin obtained melts at 208-209° C. Instead of sulfuric acid, zinc chloride, phosphoric acid or toluenesulfonic acid can also be used as a condensation agent. Condensation can also be effected by heating the components in a molten state to over 150° C. Instead of α-methoxyethylbenzene, α-acetoxyethylbenzene or α-bromomethylbenzene can also be used.

Ved analog arbeidsmåte får man føl-gende forbindelser: av 4-oksy-kumarin og a-metoksy-n-propyl -bensol-a-acetoksy-n-propylbensol eller a-brom-n-propylbensol fås 3-(a-fenyl-n-propyl)-4-oksy-kumarin (smeltepunkt 178 —179°), —av 4-oksy-kumarin og a-metoksy-n-propyl-4-metylbensol eller a-acetoksy-n-propyl-4-metyl-bensol fås 3-(a-y-tolyl-n-propyl)-4-oksy-kumarin (smeltepunkt 131 132°), av 4-oksy-kumarin og a-acetoksy-n-propyl-4-klorbensol fås 3-(a-Y-klorfenyl-ri-propyl) -4-oksy-kumarin (smeltepunkt 192— 192,5°), By working analogously, the following compounds are obtained: from 4-oxy-coumarin and a-methoxy-n-propyl-benzene-a-acetoxy-n-propylbenzene or a-bromo-n-propylbenzene, 3-(a-phenyl- n-propyl)-4-oxy-coumarin (melting point 178 —179°), —of 4-oxy-coumarin and a-methoxy-n-propyl-4-methylbenzene or a-acetoxy-n-propyl-4-methyl- benzene yields 3-(α-y-tolyl-n-propyl)-4-oxy-coumarin (melting point 131 132°), from 4-oxy-coumarin and α-acetoxy-n-propyl-4-chlorobenzene yields 3-(α-Y- chlorophenyl-ri-propyl)-4-oxy-coumarin (melting point 192— 192.5°),

av 7-metyl-4-oksy-kumarin og a-metoksy-n-propylbensol eller a-acetoksy-n-propylbensol fås 7-metyl-3-(a-fenyl-n-propyl)-4-oksy-kumarin (smeltepunkt 160—162°), av 4-oksy-kumarin og a-metoksy- eller a-acetoksy-n-butylbensol fås 3-(a-fenyl-n-butyl)-4-oksy-kumarin (smeltepunkt 200 —201°). av 4-oksy-kumarin og ct-acetoksy-etyl-4-isopropyl-behsol fås 3-[a-(4-isopropylfenyl -etyl]-4-oksy-kumarin (smeltepunkt 158 —160°). av 4-oksy-kumarin og a-metoksy-n-propyl -4-etylbensol fås 3-(a-4-etyl-fenyl)-n-propyl]-4-oksy-kumarin (smltp. 158— 160°). of 7-methyl-4-oxy-coumarin and α-methoxy-n-propylbenzene or α-acetoxy-n-propylbenzene yields 7-methyl-3-(α-phenyl-n-propyl)-4-oxy-coumarin (melting point 160—162°), from 4-oxy-coumarin and a-methoxy- or a-acetoxy-n-butylbenzene 3-(a-phenyl-n-butyl)-4-oxy-coumarin is obtained (melting point 200 —201°) . of 4-oxy-coumarin and ct-acetoxy-ethyl-4-isopropyl-behsol gives 3-[a-(4-isopropylphenyl-ethyl]-4-oxy-coumarin (melting point 158 —160°). of 4-oxy- coumarin and α-methoxy-n-propyl-4-ethylbenzene gives 3-(α-4-ethyl-phenyl)-n-propyl]-4-oxy-coumarin (m.p. 158—160°).

Eksempel 17. Example 17.

8 vektsdeler 4-oksy-kumarin og 10 vektsdeler a-oksy-hydrinden-metyleter oppvarmes noen tid ved 100° C i 5 volumdeler iseddik sammen med 1 volumdel svovelsyre av 60° Bé. Smeiten helles i vann, reaksjonsproduktet tas opp i eter, og ekstraheres fra eteroppløsningen med fortynnet natronlut. Den vandige oppløsning syres, det utfelte reaksjonsprodukt filtreres fra og omkrystalliseres fra fortynnet alkohol. Det erholdte 3-a-indanyl-4-oksy-kumarin smelter ved 195°. I stedet for a-oksy-hydrinden-metyleter kan man også anvende a-acetoksy-hydrinden eller a-klor-hydrinden. På analog måte får man med al.-a-metoksy-tetralin produktet 3-al.-a-tetralyl-4-oksy-kumarin (smeltepunkt 186 —187°). 8 parts by weight of 4-oxy-coumarin and 10 parts by weight of α-oxy-hydrindene methyl ether are heated for some time at 100° C in 5 parts by volume of glacial acetic acid together with 1 part by volume of sulfuric acid of 60° Bé. The melt is poured into water, the reaction product is taken up in ether, and extracted from the ether solution with dilute caustic soda. The aqueous solution is acidified, the precipitated reaction product is filtered off and recrystallized from dilute alcohol. The 3-α-indanyl-4-oxy-coumarin obtained melts at 195°. Instead of α-oxyhydrindene methyl ether, one can also use α-acetoxyhydrindene or α-chlorohydrindene. In an analogous way, the product 3-al.-a-tetralyl-4-oxy-coumarin is obtained with al.-α-methoxy-tetralin (melting point 186-187°).

Ved analog arbeidsmåte får man føl-gende forbindelser: av 7-metyl-4-oksy-kumarin og al.-a-acetoksy-tetralin fås 7-metyl-3-(al.-a-tetralyl) -4-oksy-kumarin (smeltepunkt 186—187°), av 7-metoksy-4-oksy-kumarin og al.-a-metoksy-tetralin fås 7-metoksy-3-(al.-a-tetralyl) -4-oksy-kumarin (smeltepunkt 190—192°). Eksempel 18. 8 vektsdeler 4-oksy-kumarin oppløses varmt i 25 volumdeler iseddik og det tilsettes 0,1 volumdel 30 pst.'s svovelsyre. Deretter blir det ved 60—70° C tildryppet 11 vektsdeler 3,4-metylen-dioksyfenyl-etyl-karbinol, og temperaturen holdes i ytterligere 1 time. Deretter helles blandingen ut i vann og reaksjonsproduktet tas opp i eter. Den eteriske oppløsning ekstraheres med 1 pst.'s natronlut, den vandige ekstrakt syres med fortynnet saltsyre, og reaksjonsproduktet filtreres fra og tørkes. Utbyttet er 12 vektsdeler 3-[a-(3',4'-metylen-dioksy-f enyl) -propyl] -4-oksy-kumarin (smeltepunkt 163—164° omkrystallisert fra fortynnet alkohol. The following compounds are obtained by an analogous working method: from 7-methyl-4-oxy-coumarin and α-acetoxy-tetralin, 7-methyl-3-(α-tetralyl)-4-oxy-coumarin is obtained (melting point 186-187°), from 7-methoxy-4-oxy-coumarin and al.-α-methoxy-tetralin is obtained 7-methoxy-3-(al.-α-tetralyl)-4-oxy-coumarin (melting point 190—192°). Example 18. 8 parts by weight of 4-oxycoumarin are dissolved hot in 25 parts by volume of glacial acetic acid and 0.1 part by volume of 30% sulfuric acid is added. Then, at 60-70° C, 11 parts by weight of 3,4-methylene-dioxyphenyl-ethyl-carbinol are added dropwise, and the temperature is maintained for a further 1 hour. The mixture is then poured into water and the reaction product is taken up in ether. The ethereal solution is extracted with 1% caustic soda, the aqueous extract is acidified with dilute hydrochloric acid, and the reaction product is filtered off and dried. The yield is 12 parts by weight of 3-[a-(3',4'-methylene-dioxy-phenyl)-propyl]-4-oxy-coumarin (melting point 163-164° recrystallized from dilute alcohol.

Claims

Process for the preparation of 4-oxy-coumarins substituted in the 3-position, characterized in that 4-oxy-coumarin or its derivatives substituted in the benzene ring are condensed with aryl-alkyl-carbinols, or with aryl-alkyl-carbinols whose alkyl residue is carbocyclic or heterocyclic connected with the aryl residue, or with compounds of the general formula

where RT is an aryl residue, R2 is an aryl or alkyl residue, and where the residue R2 — if it is an alkyl residue — can also be alicyclic or heterocyclically connected to the aryl residue Rj, and where X denotes an alkyl ether-. an acyloxy group or a halogen atom.