SE448165B - NEW PROCEDURE FOR PREPARATION OF 4-SUBSTITUTED 1,2-DIPHENYL-3,5-DIOXOPYRAZOLIDINES - Google Patents
NEW PROCEDURE FOR PREPARATION OF 4-SUBSTITUTED 1,2-DIPHENYL-3,5-DIOXOPYRAZOLIDINESInfo
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- SE448165B SE448165B SE7903095A SE7903095A SE448165B SE 448165 B SE448165 B SE 448165B SE 7903095 A SE7903095 A SE 7903095A SE 7903095 A SE7903095 A SE 7903095A SE 448165 B SE448165 B SE 448165B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C243/00—Compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/28—Two oxygen or sulfur atoms
- C07D231/30—Two oxygen or sulfur atoms attached in positions 3 and 5
- C07D231/32—Oxygen atoms
- C07D231/36—Oxygen atoms with hydrocarbon radicals, substituted by hetero atoms, attached in position 4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D317/30—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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Description
448 165 å.) vari A' betecknar väte eller en företrad hydroxylqrUPP, före- trädesvis B-metoxietoximetoxi (=MEM) gruppen med ett triaryl- fosforanderivat med den allmänna formeln R A \ c = Pí-Ar III / \ R' Ar vari R och R' har ovan angiven betydelse och vari Ar betecknar I' en (eventuellt med en inert rest såsom metyl, metoxi eller fenyl substituerad) fenylgrupp efter omröring vid rumstempera- tur och upphettning av reaktionsblandningen till 30-l00°C och att man eventuellt för att erhålla föreningar med den all- männa formeln I vari A = OH spjälkar etergruppen med milda Lewis-syror, varvid föreningen med den allmänna formeln III eventeullt framställts in situ genom avspjälkning av halogen- väte ur föreningar med den allmänna formeln: R Ar g \ <4/ x<-> ma en* P m' R, Ar vari R, R' och Ar har ovan angiven betydelse och ÄE>betecknar en halogenjon. 448 165 å.) Wherein A 'represents hydrogen or an etherified hydroxyl group, preferably the B-methoxyethoxymethoxy (= MEM) group with a triarylphosphorane derivative of the general formula RA \ c = Pí-Ar III / \ R' Ar wherein R and R 'is as defined above and wherein Ar represents I' a (optionally with an inert residue such as methyl, methoxy or phenyl substituted) phenyl group after stirring at room temperature and heating the reaction mixture to 30-100 ° C and to obtain compounds of the general formula I wherein A = OH cleaves the ether group with mild Lewis acids, the compound of the general formula III possibly being prepared in situ by cleavage of hydrogen halide from compounds of the general formula: R Ar g <4 / x <-> ma en * P m 'R, Ar wherein R, R' and Ar have the meaning given above and ÄE> denotes a halogen ion.
Som lämpliga Lewis-syror ifrågakommer speciellt TiCl4 och ZnBr2, men även ZnC12, ZnJ2, SnCl4, SnBr4, MgCl2, MgBr2 och liknande metallhalogenider kan ifrågakomma. åk 448 165 Omsättningen av föreningarna II och III kan ske i ett apro- tiskt lösningsmedel såsom dimetylformamid eller företrädes- vis dimetylsulfoxid under vattenfria betingelser.Suitable Lewis acids are especially TiCl4 and ZnBr2, but also ZnCl2, ZnJ2, SnCl4, SnBr4, MgCl2, MgBr2 and similar metal halides can be considered. The reaction of compounds II and III can take place in an aprotic solvent such as dimethylformamide or preferably dimethylsulfoxide under anhydrous conditions.
Avspjälkningen av halogenväte sker med ett lämpligt metall- reagens, såsom t.ex. natriumhydrid, natriumamid, butyllitium eller fenyllitium.The hydrogen halide is cleaved off with a suitable metal reagent, such as e.g. sodium hydride, sodium amide, butyllithium or phenyllithium.
Genomförandet av förfarandet kan t.ex. ske genom att man före- trädesvis upphettar reaktionsblandningen efter omröring vid rumstemperatur till en temperatur mellan 50-70°C, låter den kallna och efterrör vid rumstemperatur.The implementation of the procedure can e.g. This is done by preferably heating the reaction mixture after stirring at room temperature to a temperature between 50-70 ° C, allowing it to cool and stirring at room temperature.
Upparbetningen efter avslutad omsättning kan t.ex. ske genom att man häller reaktionsblandningen på is, extraherar med ett lämpat organiskt lösningsmedel såsom etylacetat eller diklorme- tan och efterföljande kolonnkromatografi eller även åter-ex- traktion av det organiska lösningsmedlet med ett basiskt vatten- haltigt medium. I det senare fallet erhålles produkten först efter surgörning med en mineralsyra (t.ex. saltsyra) och extrak- tion med ett lämpat lösningsmedel. Ytterligare rening samt även separation av de geometriska (E,Z)-isomererna kan åstadkommas genom kolonnkromatografi.The reprocessing after completion of sales can e.g. This is done by pouring the reaction mixture onto ice, extracting with a suitable organic solvent such as ethyl acetate or dichloromethane and subsequent column chromatography or even re-extraction of the organic solvent with a basic aqueous medium. In the latter case, the product is obtained only after acidification with a mineral acid (eg hydrochloric acid) and extraction with a suitable solvent. Further purification as well as separation of the geometric (E, Z) isomers can be accomplished by column chromatography.
Om A i utgångsföreningarna betecknar en företrad hydroxylgrupp- måste denna under reaktionen skyddade OH-grupp därefter friläg- gas för att föreningar med formeln I vari A = OH skall erhållas.If A in the starting compounds denotes a etherified hydroxyl group, this OH group protected during the reaction must then be exposed in order to obtain compounds of formula I in which A = OH.
Detta kan exempelvis ske genom att man spjälkar den företrade,, t.ex. i ß-metoxietoximetyl (=MEM)-eter överförda OH-gruppen efter avslutad reaktion av den företrade cyklohemiacetalen II med trifenylfosforanderivatet med formeln III med milda Lewis- syror (t.ex.TiCl4 i diklormetan). 448 165 Sådana föreningar med den allmänna formeln I vari R = CH3 och R' = COOH erhålles genom mild alkalisk förtvålning av motsva- rande ester (R = CH3, R' = COOR").This can be done, for example, by splitting the entrained ,, e.g. in the β-methoxyethoxymethyl (= MEM) ether transferred the OH group after completion of the reaction of the etherified cyclohemiacetal II with the triphenylphosphorane derivative of the formula III with mild Lewis acids (eg TiCl4 in dichloromethane). 448 165 Such compounds of the general formula I in which R = CH3 and R '= COOH are obtained by mild alkaline saponification of the corresponding ester (R = CH3, R' = COOR ").
Föreningarna med den allmänna formeln II kan på enkelt sätt er- hållas genom omlagring av motsvarande cykliska acetal med den allmänna formeln CH2-- O\ /CO-- T -- - A' IV CH - C112 - CH CH2---O \\\CO___-Ä -_ // \\ vari A' har ovan angiven betydelse. Denna omlagring kan t.ex. åstadkommas genom enkel upphettning i vattenhaltig etanol.The compounds of the general formula II can be obtained in a simple manner by rearrangement of the corresponding cyclic acetal of the general formula CH2 - O \ / CO-- T - - A 'IV CH - C112 - CH CH2 --- O \ \\ CO ___- Ä -_ // \\ wherein A 'has the meaning given above. This rearrangement can e.g. is achieved by simple heating in aqueous ethanol.
Föreningarna med den allmänna formeln IV kan å sin sida erhål- las genom reaktion av dietyl-2-(2-etylendioxietyl)malonat med formeln cH2-- o coocofl / \Cn - Ciiä -CI-I' CH2---Ö/// \\\\ V COOCZH5 5 med hydrazobensol resp. företrad p-hydroxihydrazobensol- ß-me- toxietoximetyl-(=MEM)-eter, i närvaro av en lösning av natrium i vattenfri etanol.The compounds of the general formula IV, in turn, can be obtained by reacting diethyl 2- (2-ethylenedioxyethyl) malonate of the formula cH2 - o cooco fl / \ Cn - Cii -Cl-I / \\\\ V COOCZH5 5 with hydrazobenzene resp. etherified p-hydroxyhydrazobenzene-β-methoxyethoxymethyl - (= MEM) -ether, in the presence of a solution of sodium in anhydrous ethanol.
Föreningen med formeln V kan även erhållas genom i och för sig kända åtgärder såsom t.ex. kondensation av 2-etylendioxietylbro- mid med dietylmalonat i bensol/dimetylformamid i närvaro av natriumhydrid.The compound of formula V can also be obtained by per se known measures such as e.g. condensation of 2-ethylenedioxyethyl bromide with diethyl malonate in benzene / dimethylformamide in the presence of sodium hydride.
Aldehyden med formeln IIa kan erhållas genom deketalisering av föreningen med formeln IV med A' = väte och kan t.ex.genomföras J 448 165 i vattenfri diklormetan med bortribromid.The aldehyde of formula IIa can be obtained by decetalizing the compound of formula IV with A '= hydrogen and can be carried out, for example, in anhydrous dichloromethane with boron tribromide.
Förfarandet enligt uppfinningen sker lätt och med höga utbyten utan väsentliga biprodukter då dubbelbindningen införes på önskat ställe och bildningen av disubstituerade produkter vid pyrazolidinringens C-4 ställning undvikes.The process according to the invention takes place easily and in high yields without significant by-products when the double bond is introduced at the desired site and the formation of disubstituted products at the C-4 position of the pyrazolidine ring is avoided.
Uppfinningen åskådliggöres närmare medelst följande exempel vari temperaturen avser celsiusgrader.The invention is further illustrated by the following examples in which the temperature refers to degrees Celsius.
Exempel l p;hvdroxiazobensol-3-metoxietoximetyleter(MEM) Till en omrörd suspension av 66,14 gram (l.5l6 mol) natrium- hydrid (55 procentig dispersion i mineralolja) i tetrahydro- furan (400 ml) tillsattes droppvis en lösning av p-hydroxiazo- bensol (l9l gram, 0,963 mol) i 810 ml tetrahydrofuran. Efter 15 minuters omrörning avkyldes lösningen och därefter indroppa- des vid 00 MEM-klorid íE.J. Corey, J.L. Gras och P.Ulrich, fretranearon rett., (1976) sia. 309.] (144 gram 1,156 moi) och blandningen omrördes vid denna temperatur i 30 minuter. vid rumstemperatur vidarerörde man därefter en timme,förstörde över- skottet natriumhydrid genom tillsats av vatten och koncentrera- de blandningen i vakuum. Resten upptogs i eter och tvättades i tur och ordning med vatten, 5-procentig natriumhydroxid och vatten tills den blev neutral. Eterextraktet torkades och in- dunstades under förminskat tryck. Därvid erhölls titelföreningen som tjock rödaktig olja (27l,44 gram, 98 %), som användes utan ytterligare rening.Example 1p; Hydroxyazobenzole-3-methoxyethoxymethyl ether (MEM) To a stirred suspension of 66.14 grams (1.516 mol) of sodium hydride (55% dispersion in mineral oil) in tetrahydrofuran (400 ml) was added dropwise a solution of p -hydroxyazobenzene (19 g grams, 0.963 mol) in 810 ml tetrahydrofuran. After stirring for 15 minutes, the solution was cooled and then added to 00 MEM chloride in E.J. Corey, J.L. Gras and P. Ulrich, Fretranearon ed., (1976) p. 309.] (144 grams 1.156 moi) and the mixture was stirred at this temperature for 30 minutes. at room temperature it was then stirred for one hour, the excess sodium hydride was destroyed by adding water and the mixture was concentrated in vacuo. The residue was taken up in ether and washed successively with water, 5% sodium hydroxide and water until neutral. The ether extract was dried and evaporated under reduced pressure. There was obtained the title compound as a thick reddish oil (27l, 44 grams, 98%), which was used without further purification.
Exempel 2 pïhydroxihydrazobensoleter MEM En lösning av p-hydroxiazobensol-MEM-eter (220 gram, 0,768 mol) i 1300 ml etanol hydrerades i närvaro av 2,2 gram Pd/C vid rumstemperatur och atmosfärstryck. Efter att ha avsugit beräk- nad mängd väte filtrerades lösningen och indunstades till 220 gram (99 procent) tills en tjock, gul olja kvarblev, vilken på 448 165 grund av sin lätthet för oxidation genast användes i nästa steg.Example 2 Phydrohydroxyhydrazobenzol ether MEM A solution of p-hydroxyazobenzene MEM ether (220 grams, 0.768 moles) in 1300 ml of ethanol was hydrogenated in the presence of 2.2 grams of Pd / C at room temperature and atmospheric pressure. After sucking off the calculated amount of hydrogen, the solution was filtered and evaporated to 220 grams (99 percent) until a thick, yellow oil remained, which at 448 165 due to its ease of oxidation was immediately used in the next step.
Exemgel 3 Dietyl-2-(2-etylendioxietyl)-malonat Till en omrörd suspension av 141,38 gram (3,24 mol) natrium- hydrid (55 procentig dispersion i mineralolja) i dimetylforma- mid (1300 ml) och bensol (500 ml) tillsattes droppvis dietyl- malonat (47l,8 gram, 2,94 mol). Efter omrörning vid rumstem- peratur tills H2-utvecklingen avslutats tillsattes 2-etylen- aiox1ety1bromia[$.M.Gurvich zh.obshcn. xnim., gl, zsas (19s7fl (492 gram, 2,94 mol) i 500 ml bensen och lösningen omrördes 16 timmar vid 80° . Därefter avkyldes blandningen, hälldes i ett överskott isvatten och produkten isolerades med eter. Ef- ter indunstning av det torkade extraktet erhölls 2-(2-etylen- dioxietyl)-malonat. xokpunkt los - 1os° (o,s mm).Example 3 Diethyl 2- (2-ethylenedioxyethyl) -malonate To a stirred suspension of 141.38 grams (3.24 moles) of sodium hydride (55% dispersion in mineral oil) in dimethylformamide (1300 ml) and benzene (500 ml) diethyl malonate (47l, 8 grams, 2.94 mol) was added dropwise. After stirring at room temperature until the evolution of H2 is complete, 2-ethylene-oxyethylbromia [$. M. Gurvich zh.obshcn. xnim., gl, zsas (19s7, (492 grams, 2.94 mol) in 500 ml of benzene and the solution was stirred for 16 hours at 80 °. Then the mixture was cooled, poured into an excess of ice water and the product was isolated with ether. the dried extract was obtained from 2- (2-ethylenedioxyethyl) malonate, m.p.
Analys för CllH18O6: funnet % C 53,42 H 7,42 beräknat % 53,65 7,37 Exemgel 4 4-(2-etylendioxietyl)-1,2-difenyl-3,5-dioxopyrazolidin Hydrazobensol (58,4 gram, 0,317 mol) sattes under omrörning till en natriumlösning (8,02 gram, 0,348 mol) i 480 ml vattenf fri etanol och därefter indroppades dietyl-2-(2-etylendioxi- etyl)-malonat (78,05 gram, 0,317 mol) inom loppet av 2 timmar' vid âterflödestemperatur. Blandningen upphettades ytterligareí en timme vid återflöde, lösningsmedlet indunstades gradvis till torrhet och återstoden upphettades en timme vid 1300 - 1400 under förminskat tryck (15 mm). Reaktionsprodukten kyldes, upptogs_i vatten, tvättades med eter och filtrerades därefter med aktivt kol. Lösningen surgjordes under kylning vilket gav en vit fast substans (72,95 gram, 68 procent) som torkades i g vakuum över fosforpentoxid och användes i nästa steg utan ytter- ligare rening.Analysis for C 11 H 18 O 6: Found% C 53.42 H 7.42 calculated% 53.65 7.37 Example gel 4 4- (2-ethylenedioxyethyl) -1,2-diphenyl-3,5-dioxopyrazolidine Hydrazobenzene (58.4 grams, 0.317 mol) was added with stirring to a sodium solution (8.02 grams, 0.348 moles) in 480 ml of anhydrous ethanol and then diethyl 2- (2-ethylenedioxyethyl) -malonate (78.05 grams, 0.317 moles) was added dropwise. the course of 2 hours' at reflux temperature. The mixture was heated for a further hour at reflux, the solvent was gradually evaporated to dryness and the residue was heated for one hour at 1300 - 1400 under reduced pressure (15 mm). The reaction product was cooled, taken up in water, washed with ether and then filtered with activated carbon. The solution was acidified under cooling to give a white solid (72.95 grams, 68 percent) which was dried in a vacuum over phosphorus pentoxide and used in the next step without further purification.
Smältpunkt: 1500 .Melting point: 1500.
Analys för Cl9Hl8N2O4: funnet- % C 67,71 H 5,33 N 8,23 beräknat % 67,44 5,36 8,28 448 165 Exemgel 5 4-(2-etylendioxietyl)-1-(p-MEM-oxifenyl-3,S*dioxopyrazolidin p-hydroxihydrazobensol-MEM-eter (137 gram, 0,475 mol) i 140 ml vattenfri etanol droppades under omrörning till en lösning av natrium (1092 gram, 0,475 mol) i etanol (330 ml) och därefter tilldroppades dietyl-2-(2-etylendioxietylmalonat (117 gram, 0,475 mol) i 120 ml etanol under 2 timmar vid återflödestem- peratur. Blandningen upphettades ytterligare en timme vid åter- flöde, lösningsmedlet indunstades gradvis till torrhet och åter- stoden upphettades under förminskat tryck en timme till 130 - 1400 . Reaktionsprodukten avkyldes, upptogs i vatten, tvättades med eter och filtrerades därefter över aktivt kol. Lösningen surgjordes med 10 procentig saltsyra till pH4 och den olja som avskildes avdrogs med etylacetat. Det torkade extraktet, som indunstades till torrhet kvarlämnade en oljig återstod, som upplöstes i en mättad lösning av piperazin i aceton. Det kristallina piperazinsaltet av 4-(2-etylendioxietyl)-l-(p-MEM- oxifenyl)~3,5-dioxopyrazolidin, som avskildes när blandningen fick stå filtrerades och upplöstes därefter i vatten. Efter sur- görning med isättika isolerades produkten med eter. Vid in- dunstning av det torkade extraktet bildades den önskade pyrazo- lidinen som blekgul olja (l05 gram, 50 procent), vilket var rent nog för att överföras i l,2,4,5-tetrahydro-l-(p-MEM-oxi- fenyl)-2-fenyl-3H-5-hydroxi-furoI2,3-c]-pyrazol-3-on.Analysis for C 19 H 18 N 2 O 4: Found% C 67.71 H 5.33 N 8.23 calculated% 67.44 5.36 8.28 448 165 Example gel 4- (2-ethylenedioxyethyl) -1- (p-MEM-oxyphenyl -3, S * dioxopyrazolidine p-hydroxyhydrazobenzene MEM ether (137 grams, 0.475 moles) in 140 ml of anhydrous ethanol was added dropwise with stirring to a solution of sodium (1092 grams, 0.475 moles) in ethanol (330 ml) and then diethyl was added dropwise. -2- (2-ethylenedioxyethylmalonate (117 grams, 0.475 mol) in 120 ml of ethanol for 2 hours at reflux temperature The mixture was heated for another hour at reflux, the solvent was gradually evaporated to dryness and the residue was heated under reduced pressure. The reaction product was cooled, taken up in water, washed with ether and then filtered over activated carbon. The solution was acidified with 10% hydrochloric acid to pH 4 and the separated oil was evaporated off with ethyl acetate. oily residue, which was dissolved in a saturated solution a in piperazine and acetone. The crystalline piperazine salt of 4- (2-ethylenedioxyethyl) -1- (p-MEM-oxyphenyl) -3,5-dioxopyrazolidine, which was separated when the mixture was allowed to stand, was filtered and then dissolved in water. After acidification with glacial acetic acid, the product was isolated with ether. Upon evaporation of the dried extract, the desired pyrazolidine formed as a pale yellow oil (105 grams, 50 percent), which was pure enough to transfer to 2,4,5-tetrahydro-1- (p-MEM-oxy phenyl) -2-phenyl-3H-5-hydroxy-furo [1,2,3-c] pyrazol-3-one.
Exemgel 6 1,2,4,s-tetranydro-1,2-difeny1-3H-5-hydroxi-furo[2,3-c]-pyra- zol-3-on En lösning av 4-(2-etylendioxietyl)-1,2-difenyl-3,5-dioxopyra- zolidin (5l,36 gram, O,l52 mol) i 510 ml 50 procentig vatten- haltig etanol kokades 3 timmar vid återflöde. Den fasta sub- stansen, som utkristalliserades ur den ännu heta lösningen samlades genom filtrering och torkades i vakuum. 36,66 gram (82 procent) l,2,4,5-tetrahydro-1,2-difenyl-3H-5-hydroxi-furo- [2,3-clpyrazol-3-on erhölls. smä1tpunkt= 2s7° sönaeraelning Analys för Cl7Hl4N2O3: funnet % C 69,18 H 4,75 N 9,63 % beräknat 69,37 4,80 9,52 448 165 Exemgel 7 l,2,4,5-tetrahydro-l-(p-MEM-oxifenyl)-2-fenyl-3H-5-hydroxifuro [2,3-c]-pyrazol-3-on En lösning av 4-(2-etylendioxietyl)-l-(p-MEM-oxifenyl)-2-fenyl- 3,5-dioxopyrazolidin (130 gram, 0,294 mol) i 1200 ml 75 procen- tig etanol kokades 6 timmar vid återflöde och indunstades där- efter till torrhet. Den erhållna återstoden omkristalliserades ur etylacetat och gav 66 gram (56 procent) l,2,4,5-tetrahydro- l-(p-MEM-oxifenyl)-2-fenyl-3H-5-hydroxi-furo[2,3-c]pyrazol-3- on som färglösa kristaller.Example Gel 6 1,2,4, s-tetranydro-1,2-diphenyl-3H-5-hydroxy-furo [2,3-c] -pyrazol-3-one A solution of 4- (2-ethylenedioxyethyl) -1,2-Diphenyl-3,5-dioxopyrazolidine (51, 36 grams, 0.62 mol) in 510 ml of 50% aqueous ethanol was refluxed for 3 hours. The solid which crystallized from the still hot solution was collected by filtration and dried in vacuo. 36.66 grams (82 percent) of 1,2,4,5-tetrahydro-1,2-diphenyl-3H-5-hydroxy-furo- [2,3-c] pyrazol-3-one were obtained. melting point = 2.7 ° C Preparation for C 17 H 14 N 2 O 3: found% C 69.18 H 4.75 N 9.63% calculated 69.37 4.80 9.52 448 165 Example 7 1, 2,4,5-tetrahydro-1- (p-MEM-oxyphenyl) -2-phenyl-3H-5-hydroxyfuro [2,3-c] -pyrazol-3-one A solution of 4- (2-ethylenedioxyethyl) -1- (p-MEM-oxyphenyl) -2-Phenyl-3,5-dioxopyrazolidine (130 grams, 0.294 moles) in 1200 ml of 75% ethanol was refluxed for 6 hours and then evaporated to dryness. The resulting residue was recrystallized from ethyl acetate to give 66 grams (56 percent) of 1,2,4,5-tetrahydro-1- (p-MEM-oxyphenyl) -2-phenyl-3H-5-hydroxy-furo [2,3- c] pyrazol-3-one as colorless crystals.
Smältpunkt: 2030 sönderdelning Analys för C21H22N2O6: funnet % C 62,99 H 5,49 N 6,95 beräknat % 63,31 5,57 7,03 Exemnel 8 4-(2-formylmetyl)-1,2-difenvl-2,5-dioxopyrazolidin Till en lösning av 4-(2-etylendioxietyl)-l,2-difenyl-3,5-dioxo- pyrazolidin (2,54 gram, 7,5 mmol) i 400 ml diklormetan till- sattes droppvis en lösning av bortribromid (l8,79 gram, 75 mmol) i 50 ml diklormetan vid -700 under omrörning. Vid denna tempe- ratur omrörde man ytterligare 24 timmar. Därefter lät man tem- peraturen öka till rumstemperatur och hällde därefter bland- ningen i ett överskott i isvatten.Melting point: 2030 decomposition Analysis for C 21 H 22 N 2 O 6: found% C 62.99 H 5.49 N 6.95 calculated% 63.31 5.57 7.03 Example 8 4- (2-formylmethyl) -1,2-diphenyl-2 5-Dioxopyrazolidine To a solution of 4- (2-ethylenedioxyethyl) -1,2-diphenyl-3,5-dioxopyrazolidine (2.54 grams, 7.5 mmol) in 400 ml of dichloromethane was added dropwise a solution of boron tribromide (18.79 grams, 75 mmol) in 50 mL of dichloromethane at -700 with stirring. At this temperature, the mixture was stirred for a further 24 hours. Then let the temperature rise to room temperature and then pour the mixture into an excess of ice water.
Det organiska skiktet avskildes och tvättades (NaHCO3-lösning) tills det var neutralt, torkades (Mg S04) och indunstades till torrhet.The organic layer was separated and washed (NaHCO 3 solution) until neutral, dried (Mg SO 4) and evaporated to dryness.
Den sega återstoden kristalliserades ur etyleter-diklormetan (8:2) och gav 0,7 gram (3l,7 procent) av den önskade pyrazoli- dinen som färglös fast substans. smältpunkt: 24o-242° .The tough residue was crystallized from ethyl ether-dichloromethane (8: 2) to give 0.7 grams (31.7 percent) of the desired pyrazolidine as a colorless solid. melting point: 24o-242 °.
Analys för' cl7H14N2o3= funnet 9 c 69,54 a 4,92 N 9,44 beräknat % 69,37 4,80 9,52 Jf 448 165 Exemgel 9 4-(3-metyl-2-butenyl)-1,2-difenyl-3,5-dioxopyrazolidin En lösning av isopropyl-trifenylfosfoniumjodid (45,24 gram, 0,1 mol) [G.Wittig und D.Wittenberg, Ann., 606, l (l957)] i 180 ml dimetylsulfoxid sattes droppvis till en omrörd suspen- sion av natriummetylsulfinylmetid vid 20-250 (R.Greenwald, M.Chaykovsky, und E.J. Corey, J. Org. Chem., volym 28 (1963) sid. ll28) som framställdes in situ av 4,15 gram (0,095 mol) av en 55 procentig dispersion av natriumhydrid i mineralolja och 120 ml dimetylsulfoxid. Blandningen omrördes 30 minuter vid rumstemperatur och därefter tillsattes portionsvis l,2,4, 5-tetrahydro-l,2-difenyl-3H-5-hydroxi-furo[2,3-c]PYrazol-3-on (14 gram, 0,047 mol). Blandningen omrördes 2 timmar vid rums- temperatur och upphettades därefter ytterligare en timme till 7o° .Analysis for C 17 H 14 N 2 O 3 = found 9 c 69.54 a 4.92 N 9.44 calculated% 69.37 4.80 9.52 C 448 165 Example gel 9 4- (3-methyl-2-butenyl) -1.2 -diphenyl-3,5-dioxopyrazolidine A solution of isopropyl-triphenylphosphonium iodide (45.24 grams, 0.1 mol) [G. Wittig and D. Wittenberg, Ann., 606, 1 (1957)] in 180 ml of dimethyl sulfoxide was added dropwise. to a stirred suspension of sodium methylsulfinylmethide at 20-250 (R. Greenwald, M. Chaykovsky, and EJ Corey, J. Org. Chem., Volume 28 (1963) p. 1128) which was prepared in situ of 4.15 grams (0.095 mol) of a 55% dispersion of sodium hydride in mineral oil and 120 ml of dimethyl sulfoxide. The mixture was stirred for 30 minutes at room temperature and then 1,2,4,5-tetrahydro-1,2-diphenyl-3H-5-hydroxy-furo [2,3-c] PYrazol-3-one (14 grams, 0.047) was added portionwise. mole). The mixture was stirred for 2 hours at room temperature and then heated for another hour at 70 °.
Efter 16 timmars omrörning vid rumstemperatur hälldes reak- tionsblandningen i ett överskott vatten och extraherades med diklormetan. Den organiska fasen avskildes, tvättades (H20), torkades (MgS04) och indunstades därefter till torrhet. Den erhållna återstoden löstes i bensen och adsorberades på en kiselgelkolonn. Elution med 10 procentig aceton i bensen gav,f 8,79 gram (58,4 procent) av den önskade pyrazolidinen som _¿ färglös fast substans. § smä1cpunkt= 155 - 1s7° _ Analys för CZOHZONZOZ: funnet % C 75,20 H 6,23 N 8,64 beräknat % 74,98 6,29 8,74 Exemgel 10 4-(2-propenyl)-1,2-difenyl-3,5-dioxopyrazolidin Denna förening framställdes på samma sätt som beskrivits i exempel 9, genom att man utgick från l,2,4,5-tetrahydro-l,2- difenyl-3H-5-hydroxi-furo[2,3-c]-pyrazol-3-on (5,88 gram, 0,02 mol) och metyltrifenylfosfoniumjodid {C.H.Collins och G.S. nammåna, J, org. chem., volym gg, sid. 1434 (196o)1 (17,7s gram, 0,044 mol) och använder natriummetylsulfinylmetid (0,04 mol) ii dimetylsulfoxid (framställd såsom beskrivits ovan). Titelför- 448 165 10 eningen erhölls efter kolonnkromatografi på silikagel (10 pro- cent aceton i bensen) som färglös fast substans (64,5 procent).After stirring for 16 hours at room temperature, the reaction mixture was poured into excess water and extracted with dichloromethane. The organic phase was separated, washed (H 2 O), dried (MgSO 4) and then evaporated to dryness. The resulting residue was dissolved in benzene and adsorbed on a silica gel column. Elution with 10% acetone in benzene gave 8.79 grams (58.4 percent) of the desired pyrazolidine as a colorless solid. § m.p. -diphenyl-3,5-dioxopyrazolidine This compound was prepared in the same manner as described in Example 9, starting from 1,2,4,5-tetrahydro-1,2-diphenyl-3H-5-hydroxy-furo [2 , 3-c] -pyrazol-3-one (5.88 grams, 0.02 mol) and methyltriphenylphosphonium iodide {CHCollins and GS nammåna, J, org. chem., volume gg, p. 1434 (196o) 1 (17.7s grams, 0.044 mol) and uses sodium methylsulfinylmethide (0.04 moles) in dimethylsulfoxide (prepared as described above). The title compound was obtained after column chromatography on silica gel (10% acetone in benzene) as a colorless solid (64.5%).
Smältpunkt: 133 - 1350 . (Et0H 95 procent).Melting point: 133 - 1350. (EtOH 95 percent).
Analys för Cl8Hl6N2O2: funnet % C 74,12 H 5,63 N 9,37 beräknat . 73,95 5,52 9,58 Q) \0 Exemoel ll (E,Z)~4-(2-butenyl)-l,2-difenyl-3,5-dioxopyrazolidin Denna förening framställdes såsom beskrivits i exempel 9 genom att man utgick från l,2,4,5-tetrahydro-l,2-difenyl-3H-5-hydroxi- furo-[2,3-c]-pyrazol-3-on (5,88 gram, 0,02 mol) och etyltrife- nylfosfonbromid (l6,33 gram, 0,044 mol) [G.Wittig und D. Wittenberg Ann., volym 606, sid. l (l957)] varvid natriumme- tylsulfinylmetid (0,04 mol) i dimetylsulfoxid, framställd på ovan beskrivet sätt, användes. Föreningen erhölls efter kolonn- kromatografi på silikagel (lO procent aceton i bensen) som blandning av E- och Z-formerna, varvid Z-isomeren övervägde (60 procent). Smältpunkt: l67° (EtOH/H20 l:l) literatursmält- punkt: 1280 för föreningen, som erhölls på sedvanlig malonat- hydrazobensenväg. 4 Analys för Cl9Hl8N2O2: funnet % C 74,32 H 5,87 N 9,22 beräknat % 74,49 5,92 9,15 Exemnel 12 (E,Z)-4-(3-fenyl-2-propenyl)-l,2-difenyl-3,5-dioxopvrazolidin Denna förening framställdes på det i exempel 9 beskrivna sättet, varvid man utgick från 1,2,4,5-tetrahydro-l,2-difenyl-3H-5-hy- droxi-furo[2,3-c]-pyrazol-3-on (5,88 gram, 0,02 mol) och ben- syltrifenylfosfonklorid (l7,ll gram, 0,044 mol) [G. Wittig och M.Schöllkopf, Chem. Ber. volym 87, sid. 1318 (l954)] och natri- ummetylsulfinylmetid (0,04 mol) i dimetylsulfoxid, framställd på ovan beskrivet sätt, användes. Föreningen erhölls som råma- terial i 64 procentigt utbyte.Analysis for C 18 H 16 N 2 O 2: found% C 74.12 H 5.63 N 9.37 calculated. 73.95 5.52 9.58 Q) \ 0 Exemoel II (E, Z) ~ 4- (2-butenyl) -1,2-diphenyl-3,5-dioxopyrazolidine This compound was prepared as described in Example 9 by starting from 1,2,4,5-tetrahydro-1,2-diphenyl-3H-5-hydroxyfuro- [2,3-c] pyrazol-3-one (5.88 grams, 0.02 mol ) and ethyltriphenylphosphonate bromide (16.33 grams, 0.044 moles) [G. Wittig and D. Wittenberg Ann., Volume 606, p. 1 (1957)] using sodium methylsulfinylmethide (0.04 mol) in dimethylsulfoxide, prepared as described above. The compound was obtained after column chromatography on silica gel (10 percent acetone in benzene) as a mixture of the E and Z forms, with the Z isomer predominating (60 percent). Melting point: 167 ° (EtOH / H 2 O 1: 1) Literary melting point: 1280 for the compound obtained by conventional malonate hydrazobenzene route. Analysis for C 19 H 18 N 2 O 2: Found% C 74.32 H 5.87 N 9.22 calculated% 74.49 5.92 9.15 Example 12 (E, Z) -4- (3-phenyl-2-propenyl) - 1,2-Diphenyl-3,5-dioxopyrazolidine This compound was prepared in the manner described in Example 9 starting from 1,2,4,5-tetrahydro-1,2-diphenyl-3H-5-hydroxy furo [2,3-c] -pyrazol-3-one (5.88 grams, 0.02 moles) and benzyltriphenylphosphonium chloride (17.1 grams, 0.044 moles) [G. Wittig and M. Schöllkopf, Chem. Ber. volume 87, p. 1318 (1954)] and sodium methylsulfinylmethide (0.04 mol) in dimethylsulfoxide, prepared as described above, were used. The compound was obtained as a raw material in 64 percent yield.
Z- och E-formerna kunde separeras genom kolonnkromatografi på silikagel (10 procent aceton i bensen). (Z)-isomer: smäitpunkn 124° (ston 95°). *' 448 165 ll Analys för C24H2oN2O2: funnet C 78,29 H 5,31 N 7,48 beräknat % 78,23 5,47 7,50 o\° (E)-isomer= smäitpunkt 133° (ston 9s°) C24H2ON2O2: funnet o\0 C 78,42 H 5,54 N 7,46 beräknat % 78,23 5,47 7,60 Exemgel 13 (E,Z)-4-(3-karbetoxi-2-butenyl)-1,2-difenyl-3,5-dioxooyrazolidin En blandning av a-karbetoxietyliden-trifenylfosforanfO. Isler, Helv.Chim.Acta, volym 49, sid. 1242 (l957E (63,53 gram, 0,175 mol) och 1,2,4,5-tetrahydro-l,2-difeny1-3H-5-hydroxi-furo [2,3-clpyrazol-3-an (26 gram, o,o8s mal) 1 4oo mi vattenfri ai- metylsulfoxid omrördes en timme vid rumstemperatur och upphetta- des ytterligare en timme till 60°. Då reaktionsblandningen rörts 15 timmar vid rumstemperatur, hälldes den i ett överskott vatten och extraherades med etylacetat. Den organiska fasen avskildes och extraherades flera gånger med en vattenhaltig 5 procentig piperazinlösning; Det förenade vattenhaltiga extrak- ten surgjordes till pH 8 med 10 procentig saltsyra och den vax- artade fasta substansen, som avskildes, avfiltrerades och kasta- des. Den filtrerade lösningen behandlades med aktivt kol, sur- gjordes därefter till pH 5,5 och extraherades med etylacetat.The Z and E forms could be separated by column chromatography on silica gel (10 percent acetone in benzene). (Z) -isomer: melting point 124 ° (ston 95 °). 448 165 μl Analysis for C 24 H 20 N 2 O 2: found C 78.29 H 5.31 N 7.48 calculated% 78.23 5.47 7.50 o \ ° (E) -isomer = melting point 133 ° (mone 9s °) C24H2ON2O2: found o \ 0 C 78.42 H 5.54 N 7.46 calculated% 78.23 5.47 7.60 Example gel 13 (E, Z) -4- (3-carbethoxy-2-butenyl) -1 , 2-diphenyl-3,5-dioxooyrazolidine A mixture of α-carbethoxyethylidene-triphenylphosphorane. Isler, Helv.Chim.Acta, volume 49, p. 1242 (1957E (63.53 grams, 0.175 moles) and 1,2,4,5-tetrahydro-1,2-diphenyl-3H-5-hydroxy-furo [2,3-c] pyrazol-3-one (26 grams, The oil mixture was stirred for one hour at room temperature and heated for a further hour at 60 DEG C. When the reaction mixture was stirred for 15 hours at room temperature, it was poured into excess water and extracted with ethyl acetate. The combined aqueous extracts were acidified to pH 8 with 10% hydrochloric acid and the waxy solid which was separated was filtered off and discarded. The filtered solution was treated with activated carbon. , was then acidified to pH 5.5 and extracted with ethyl acetate.
Efter indunstning av det torkade extraktet erhölls den råa iso- mera blandningen av (E)- och (Z)-4-(3-karbetoxi-2-butenyl)-l,2- difenyl-3,5-dioxopyrazolidin som en brun, tjock olja, som löstes i aceton och renades genom sitt 2-amino-2-tiazolinsalt.After evaporation of the dried extract, the crude isomeric mixture of (E) - and (Z) -4- (3-carbethoxy-2-butenyl) -1,2-diphenyl-3,5-dioxopyrazolidine was obtained as a brown, thick oil, which was dissolved in acetone and purified by its 2-amino-2-thiazoline salt.
Upparbetningen av detta salt som skedde analogt med exempel 5 gav efter extraktion med etylacetat och indunstning av det tor- kade extraktet 19,5 gram av en oljig blandning av den önskade pyrazolidinen vari (E)-formen övervägde. Denna blandning upp- löstes i bensen och adsorberades på en kiselgelkolonn. Elution med 10 procentigtetylacetat i bensen gav 1,36 gram (4 procent) av (Z)-formen som färglös fast substans. smä1tpunkt= 1s1° . 448 165 12 Analys för C22H22N204: funnet % C 69,59 H 5,97 N l7,02 beräknat % 69,82 5,86 16,91 Den ytterligare elueringen med samma medel gav en mellanfrak- tion, som bestod av en blandning av 2 isomerer och därefter en fraktion av 14 gram (42 procent) av (E)-formen som färglös fast substans, som omkristalliserades ur cyklohexan. smälcpunkt: 93° .The work-up of this salt, which took place analogously to Example 5, after extraction with ethyl acetate and evaporation of the dried extract gave 19.5 grams of an oily mixture of the desired pyrazolidine in which the (E) form predominated. This mixture was dissolved in benzene and adsorbed on a silica gel column. Elution with 10% ethyl acetate in benzene gave 1.36 grams (4 percent) of the (Z) form as a colorless solid. melting point = 1s1 °. Analysis for C 22 H 22 N 2 O 4: found% C 69.59 H 5.97 N 17.02 calculated% 69.82 5.86 16.91 The further elution with the same agent gave an intermediate fraction, which consisted of a mixture of 2 isomers and then a fraction of 14 grams (42 percent) of the (E) form as a colorless solid, which was recrystallized from cyclohexane. melting point: 93 °.
Analys för C22H22N204: funnet % C 69,87 H 5,81 N 16,80 beräknat % 69,82 5,86 l6,9l Exempel 14 (E,Z)-4-(3-karbetoxi-2-butenyl)-1,2-difenyl-3,5-dioxopyrazolidin Denna förening framställdes på det i exempel 13 beskrivna sät- tet, varvid man utgick från d-karbetoxietylidentrifenylfosforan (l,46 gram, 4 mmol) och 4-(2-formylmetyl)-1,2-difenyl-3,5-di- oxopyrazolidin (O,59 gram, 2 mmol) i 12 ml dimetylsulfoxid och erhöll 0,24 gram (3l,7 procent) av titelföreningen.Analysis for C 22 H 22 N 2 O 4: found% C 69.87 H 5.81 N 16.80 calculated% 69.82 5.86 16.91 Example 14 (E, Z) -4- (3-carbethoxy-2-butenyl) -1 , 2-diphenyl-3,5-dioxopyrazolidine This compound was prepared in the manner described in Example 13 starting from d-carbethoxyethylidene triphenylphosphorane (1.46 grams, 4 mmol) and 4- (2-formylmethyl) -1, 2-diphenyl-3,5-dioxopyrazolidine (0.5 g, 2 mmol) in 12 mL of dimethyl sulfoxide to give 0.24 g (31.7 percent) of the title compound.
Fysikaliska-kemiska och analytiska data och även E/Z~isomerer- förhållandet var nästan identiskt med i föregående exempel er- hållna data.Physico-chemical and analytical data and also the E / Z ~ isomer ratio were almost identical to the data obtained in the previous example.
Exempel 15 .Example 15.
(E,Z)-4-(3-karbetoxi-2-butenyl)-1-(p-MEM-oxifenyl)-2-fenyl-3,5- dioxopyrazolidin En blandning av drkarbetoxietylidentrifenylfosforan (l4,49 gram, 0,04 mol) och 1,2,4,5-tetrahydro-l-(p-MEM-oxifenyl)-2-fenyl-3H- 5-hydroxi-furo[2,3-c]-pyrazol-3-on (l5,96 gram, 0,04 mol) i 90 ml vattenfri dimetylsulfoxid fick reagera på det i exempel 13 beskrivna sättet. Därefter hälldes reaktionsblandningen i ett överskott vatten, extraherades med etylacetat och extraherades ännu en gång med en 5 procentig vattenhaltig piperazinlösning.(E, Z) -4- (3-Carbethoxy-2-butenyl) -1- (p-MEM-oxyphenyl) -2-phenyl-3,5-dioxopyrazolidine A mixture of carbethoxyethylidene triphenylphosphorane (14.49 grams, 0.04 mol) and 1,2,4,5-tetrahydro-1- (p-MEM-oxyphenyl) -2-phenyl-3H-5-hydroxy-furo [2,3-c] -pyrazol-3-one (15, 96 grams, 0.04 mol) in 90 ml of anhydrous dimethyl sulfoxide were allowed to react in the manner described in Example 13. Then the reaction mixture was poured into an excess of water, extracted with ethyl acetate and extracted once more with a 5% aqueous piperazine solution.
Efter surgörning av vattenfasen till pH 6, isolerades produkten med eter och gav, efter indunstning av det torkade extraktet 10,2 gram av en oljig blandning av den önskade pyrazolidinen, som hade övervägande (E)-form. Blandningen upplöstes i bensen och adsorberades på en kiselgelkolonn. Elueringen med diklorme- ~ LJ; 448 165 13 tan gav 0,58 gram (3 procent) av (Z)-formen som gul olja. Den ytterligare elueringen gav, efter en fraktion, som bestod av en blandning av två isomerer, en fraktion,av 6,05 gram (3l pro- cent) av (E)-isomeren som gul olja.After acidifying the aqueous phase to pH 6, the product was isolated with ether to give, after evaporation of the dried extract, 10.2 grams of an oily mixture of the desired pyrazolidine, which had a predominant (E) form. The mixture was dissolved in benzene and adsorbed on a silica gel column. The elution with dichloromel- ~ LJ; 448 165 13 tan gave 0.58 grams (3 percent) of the (Z) form as yellow oil. The further elution gave, after a fraction consisting of a mixture of two isomers, a fraction of 6.05 grams (3%) of the (E) -isomer as a yellow oil.
Exempel 16 (E)-4-(3-karbetoxi-2-butenyl)-l-(p-hydroxifenyl)-2-fenyl-3,5- dioxopyrazolidin Till en omrörd lösning av titaniumtetraklorid (77,26 gram, 0,407 mol) i 750 ml diklormetan tillsattes droppvis vid Oo en lösning av (E)-4-(3-karbetoxi-2-butenyl)-l-(p-MEM-oxifenyl)-2- fenyl-3,5-dioxopyrazolidin, beredd såsom i exempel 15, (30,3 gram, 0,081 mol) i 400 ml diklormetan. Man efterrörde en timme och hällde blandningen i ett överskott isvatten. Den organiska fasen avskildes, torkades och indunstades och gav en oljig åter- stod, som löstes i diklormetan och adsorberades på en kiselgel- kolonn. Eluering i 10 procentig metanol i diklormetan gav 25,4 gram (79 procent) av titelföreningen som färglös fast substans. smältpunkt; 7o - 74° .Example 16 (E) -4- (3-Carbethoxy-2-butenyl) -1- (p-hydroxyphenyl) -2-phenyl-3,5-dioxopyrazolidine To a stirred solution of titanium tetrachloride (77.26 grams, 0.407 mol) In 750 ml of dichloromethane a solution of (E) -4- (3-carbethoxy-2-butenyl) -1- (p-MEM-oxyphenyl) -2-phenyl-3,5-dioxopyrazolidine, prepared as in Example 15, (30.3 grams, 0.081 mol) in 400 ml of dichloromethane. Stir for an hour and pour the mixture into an excess of ice water. The organic phase was separated, dried and evaporated to give an oily residue, which was dissolved in dichloromethane and adsorbed on a silica gel column. Elution in 10% methanol in dichloromethane gave 25.4 grams (79%) of the title compound as a colorless solid. melting point; 7o - 74 °.
Analys för C22H22N205: funnet % C 66,84 H 5,51 N 6,92 beräknat % 66,99 5,62 7,10 Exempel 17 (E)-4-(3-karboxi-2-butenyl)-1,2-difenyl-3,5-dioxopyrazolidin En lösning av (E)-4-(3-karbetoxi-2-butenyl)-l,2-difenyl-3,5- dioxopyrazolidin, beredd såsom beskrivits i exempel 13, (2,25 gram, 5,28 mol) i l0 ml l0 procentig natriumhydroxid omrördes 30 minuter vid rumstemperatur och surgjordes därefter med 10 procentig saltsyra. Den utfallande produkten isolerades med di- klormetan och gav efter indunstning av det torkade extraktet en gummiartad återstod, som kristalliserades ur etyleter. (l,05 gram, 56,75 procent).Analysis for C 22 H 22 N 2 O 5: found% C 66.84 H 5.51 N 6.92 calculated% 66.99 5.62 7.10 Example 17 (E) -4- (3-carboxy-2-butenyl) -1.2 -diphenyl-3,5-dioxopyrazolidine A solution of (E) -4- (3-carbethoxy-2-butenyl) -1,2-diphenyl-3,5-dioxopyrazolidine, prepared as described in Example 13, (2,25 grams, 5.28 mol) in 10 ml of 10% sodium hydroxide was stirred for 30 minutes at room temperature and then acidified with 10% hydrochloric acid. The precipitated product was isolated with dichloromethane to give, after evaporation of the dried extract, a gummy residue which crystallized from ethyl ether. (1.05 grams, 56.75 percent).
Smältpunkt: 1410 .Melting point: 1410.
A“alYS för CzoH1aNz°4* funnet % C 68 28 H 5 19 N 7 97 I l I beräknat % 63,55 5,13 8,00 448 165 14 ln) Exempel 18 (Z)-4-(3-karboxi-2-butenyl)-l,2-difenyl-3,5-dioxopyrazolidin *I Denna förening bereddes på det i exempel 17 beskrivna sättet genom hydrolys av (Z)-4-(3-karbetoxi-2-butenyl)-l,2-difeny1- 3,5-dioxopyrazolidin, framställd såsom i exempel 13, (1 gram, 2,6 mmol) med 10 procentig natriumhydroxid (20 ml). Efter sed- vanlig upparbetning kristalliserades föreningen ur etyleter och gav 0,6 gram (61 procent) av den önskade pyrazolidinen som färg- lösa kristaller.Al 2 O 3 for C 20 H 11 N 2 O 4 * found% C 68 28 H 5 19 N 7 97 I l I calculated% 63.55 5.13 8.00 448 165 14 ln) Example 18 (Z) -4- (3-carboxy -2-butenyl) -1,2-diphenyl-3,5-dioxopyrazolidine * This compound was prepared in the manner described in Example 17 by hydrolysis of (Z) -4- (3-carbethoxy-2-butenyl) -1, 2-Diphenyl-3,5-dioxopyrazolidine, prepared as in Example 13, (1 gram, 2.6 mmol) with 10% sodium hydroxide (20 mL). After the usual work-up, the compound crystallized from ethyl ether to give 0.6 grams (61 percent) of the desired pyrazolidine as colorless crystals.
Smältpunkt: 650 .Melting point: 650.
Analys för C2oHl8N204 funnet % C 68,37 H 5,28 N 7,88 beräknat % 68,56 5,28 7,88 Exempel 19 (E)-4-(3-karboxi-2-butenyl)-1-(p-hydroxifenyl)-2-fenyl-3,5-di- oxo-pyrazolidin Denna förening framställdes på samma sätt genom hydrolys av (E)-4-(3-karbetoxi-2-butenyl)-l-(p-hydroxifenyl)-2-fenyl-3,5- ' dioxopyrazolidin, framställd enligt exempel 16, (10 gram, 25 mmol) med 10 procentig natriumhydroxid (200 ml). Den erhållna föreningen omkristalliserades ur acetonitril. Denna gav 2,15 gram (23,2 procent) av titelföreningen som färglösa kristaller. smälfipunkt= 17o° .Analysis for C 20 H 18 N 2 O 4 found% C 68.37 H 5.28 N 7.88 calculated% 68.56 5.28 7.88 Example 19 (E) -4- (3-carboxy-2-butenyl) -1- (p -hydroxyphenyl) -2-phenyl-3,5-dioxo-pyrazolidine This compound was prepared in the same manner by hydrolysis of (E) -4- (3-carbethoxy-2-butenyl) -1- (p-hydroxyphenyl) - 2-Phenyl-3,5-dioxopyrazolidine, prepared according to Example 16, (10 grams, 25 mmol) with 10% sodium hydroxide (200 mL). The obtained compound was recrystallized from acetonitrile. This gave 2.15 grams (23.2 percent) of the title compound as colorless crystals. narrow fi point = 17o °.
Analys för C2OHl8NåO5 funnet % C 65,30 H 5,01 N 7,61 beräknat % 65,56 4,95 7,66Analysis for C 2 OH 18 NaO 5 found% C 65.30 H 5.01 N 7.61 calculated% 65.56 4.95 7.66
Claims (2)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19782815302 DE2815302A1 (en) | 1978-04-08 | 1978-04-08 | NEW PROCESS FOR THE PREPARATION OF 4-SUBSTITUTED 1,2-DIPHENYL-3,5-DIOXOPYRAZOLIDINES |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SE7903095L SE7903095L (en) | 1979-10-09 |
| SE448165B true SE448165B (en) | 1987-01-26 |
Family
ID=6036514
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SE7903095A SE448165B (en) | 1978-04-08 | 1979-04-06 | NEW PROCEDURE FOR PREPARATION OF 4-SUBSTITUTED 1,2-DIPHENYL-3,5-DIOXOPYRAZOLIDINES |
Country Status (19)
| Country | Link |
|---|---|
| JP (1) | JPS54141770A (en) |
| AR (1) | AR220377A1 (en) |
| AT (1) | AT370726B (en) |
| CA (1) | CA1134834A (en) |
| CH (1) | CH639074A5 (en) |
| DE (1) | DE2815302A1 (en) |
| DK (1) | DK143279A (en) |
| ES (1) | ES479422A1 (en) |
| FI (1) | FI70707C (en) |
| FR (1) | FR2421886A1 (en) |
| GR (1) | GR66638B (en) |
| IN (1) | IN150827B (en) |
| IT (1) | IT1193754B (en) |
| NL (1) | NL7902731A (en) |
| NO (1) | NO152006C (en) |
| PL (1) | PL117473B1 (en) |
| PT (1) | PT69449A (en) |
| SE (1) | SE448165B (en) |
| YU (1) | YU41152B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02166236A (en) * | 1988-12-19 | 1990-06-26 | Kawasaki Steel Corp | Floater having side plate |
| JPH0331465A (en) * | 1989-06-27 | 1991-02-12 | Kawasaki Steel Corp | Method for correcting meandering in floater |
-
1978
- 1978-04-08 DE DE19782815302 patent/DE2815302A1/en not_active Withdrawn
-
1979
- 1979-03-26 IN IN198/DEL/79A patent/IN150827B/en unknown
- 1979-03-28 GR GR58712A patent/GR66638B/el unknown
- 1979-03-30 AT AT0236979A patent/AT370726B/en not_active IP Right Cessation
- 1979-04-02 AR AR276032A patent/AR220377A1/en active
- 1979-04-04 CH CH313779A patent/CH639074A5/en not_active IP Right Cessation
- 1979-04-05 YU YU815/79A patent/YU41152B/en unknown
- 1979-04-06 SE SE7903095A patent/SE448165B/en not_active IP Right Cessation
- 1979-04-06 JP JP4188579A patent/JPS54141770A/en active Granted
- 1979-04-06 FR FR7908855A patent/FR2421886A1/en active Granted
- 1979-04-06 PT PT69449A patent/PT69449A/en unknown
- 1979-04-06 FI FI791139A patent/FI70707C/en not_active IP Right Cessation
- 1979-04-06 DK DK143279A patent/DK143279A/en not_active IP Right Cessation
- 1979-04-06 NO NO791161A patent/NO152006C/en unknown
- 1979-04-06 NL NL7902731A patent/NL7902731A/en unknown
- 1979-04-06 CA CA000325093A patent/CA1134834A/en not_active Expired
- 1979-04-06 PL PL1979214738A patent/PL117473B1/en unknown
- 1979-04-06 IT IT48654/79A patent/IT1193754B/en active
- 1979-04-07 ES ES479422A patent/ES479422A1/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| DE2815302A1 (en) | 1979-10-18 |
| NO152006B (en) | 1985-04-09 |
| AT370726B (en) | 1983-04-25 |
| ATA236979A (en) | 1982-09-15 |
| IT1193754B (en) | 1988-08-24 |
| IT7948654A0 (en) | 1979-04-06 |
| JPS6213951B2 (en) | 1987-03-30 |
| DK143279A (en) | 1979-10-09 |
| CH639074A5 (en) | 1983-10-31 |
| AR220377A1 (en) | 1980-10-31 |
| JPS54141770A (en) | 1979-11-05 |
| PL214738A1 (en) | 1980-06-16 |
| FR2421886A1 (en) | 1979-11-02 |
| FI70707B (en) | 1986-06-26 |
| PT69449A (en) | 1979-05-01 |
| SE7903095L (en) | 1979-10-09 |
| YU41152B (en) | 1986-12-31 |
| FI70707C (en) | 1986-10-06 |
| GR66638B (en) | 1981-04-03 |
| NL7902731A (en) | 1979-10-10 |
| CA1134834A (en) | 1982-11-02 |
| ES479422A1 (en) | 1980-02-01 |
| NO152006C (en) | 1985-07-17 |
| FI791139A (en) | 1979-10-09 |
| FR2421886B1 (en) | 1983-09-09 |
| PL117473B1 (en) | 1981-08-31 |
| YU81579A (en) | 1983-06-30 |
| NO791161L (en) | 1979-10-09 |
| IN150827B (en) | 1982-12-25 |
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