PL111601B1 - Process for preparing novel 2,3-diacyl derivatives of 1,2,3,4-tetrahydrophthalazine - Google Patents

Process for preparing novel 2,3-diacyl derivatives of 1,2,3,4-tetrahydrophthalazine Download PDF

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Publication number
PL111601B1
PL111601B1 PL20356577A PL20356577A PL111601B1 PL 111601 B1 PL111601 B1 PL 111601B1 PL 20356577 A PL20356577 A PL 20356577A PL 20356577 A PL20356577 A PL 20356577A PL 111601 B1 PL111601 B1 PL 111601B1
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parts
weight
tetrahydrophthalazine
preparing novel
temperature
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PL20356577A
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Polish (pl)
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PL203565A1 (en
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Stefan Groszkowski
Barbara Wesolowska
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Akad Medyczna
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  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Description

Przedmiotem wynalazku jest apasób otirzymywa- nia nowych 2,3-'dwuaicylowyoh pochodnych 1,2,3,4- -tetrahyldiroftailazyny o wzorze ogólnym przedsta¬ wionym na rysunku, w którylm R oznaicza grupe metylowa, izoiprolpylowa lub tert.-butylowa.Pochodne te zastosowano dio syntezy chlorowo¬ dorku 1,2,3,4-tetrahyd'roiftalaizyny, którego uzywa sie jako odczynnika do oznajozainia formaldehydu oraz jako produktu posredniego do wytwarzania zwiazków o dzialaniu fafrrciakoldgLaznym, szczegól-- njiie na uklad nerkowy i ulklad krajzenia.Sposobem wedlug wynialaizku zwiazki o wzorze ogólmym przedstawionym na rysunku otrzymuje sie na drodze kondensacji jiedinopotasiolwych soli 1,2-dwuaicylOhydraizyn z a,a%dwuchlioirowco-o-ksy- lenami, korzystnie jiednopotasowej isoli 1,2-dwuace- tylohydlraizyny z a,a'ndwuibromo-o-(kisy]ielnelm, w sro¬ dowisku dwumetyloformalmidu poczatkowo w tem¬ peraturze 20—80°C, kotnzyistniie 60°C, a nastepnie w temperaturze wrzenia roztworu.Ponizsze przyklady objasniaja blizej sposób we¬ dlug wynalazku.Przyklad I. 61,68 czesci wagowych jednopto- tasowej soli l,2-dwuaicetyliohyd,razyny w 1000. cze- sciiaiclh objetosciowych dwumetylofoirmamMu ogrze¬ wa sie do temperatury 60°C i w tej temperaturze wkirapla w ciagu 3 godzin przy ciaglym mieszaniu uprzednio przygotowainy roztwór a,a'-dwulbriomo-o- 10 15 20 30 -ksylenu 52,79 czesoi wagowych w 500 czesciach objetosciowych diwumetylafortmaimidu.Po wkroipleiniu oigrzewa sie jeszcze w tempera¬ turze wilzania przez 3 /godziny. Z ostudzonej mie¬ szaniny odsacza sie wydzielony bromek piotaisowy i z praelsaozu oddestylowuje ,pod zmniejszonym cisnieniem dwumietylioformalmid* Pozostalosc ma- ceruje sie woda.i saczy. Osad przemywa sie woda (do momentu gdy widmo IR osadu oie wykazuje obecnosci paisima NH) i suiszy.Otrzylmuije sie 32,31 czesoi wagowych (74,02% wy¬ dajnosci teoretycznej) 2,3-diwuaGetylo-!l,!2,3,4-t'etra- hydinoftalazyny o temperaturze tqpniielniia 149— 153°C. Po krystalizacji ,z. izoprojpanjolu otrzymuje sie 30,50 czesci wagowych (69,87% wyidajjnosci teo- iretycznej) zwiazku topniejacego w temperaturze 1511,5—il5;2°C.P, r z y k l ad II. Uzywaijajc 61,68 czesci wagowych jednqpota)soiwe!j soli l,2Hdwua|cetyldhydirazyiny i 35,01 czesci wagowych a,a'-idtwuichloro-o-klsylienu póisitepuje sie w sposób opisany w przykladzie I.Po krystalizacji z izopropainolu otrzymuje sie 28,22 czesci waigowych (64,65°/© wydaijnoisici teorle- tycznej) 2,3-tdwuatoetylo-il,2,3,4-tetrahydlroiftalaizyny o temperaturze topnienia 151,5—U52°C.Przyklad III. Uzywajac 84,13 czesci wago¬ wych jednopotaisowej soli l;,2-dwuizolbutyryloihy- drazyny i 52,79 ozesoi wagowych a,«'-dwuiblro(mjO-o- -ksylenu postepuje sie jak w pirzyklaldzie I do 111 601111 601 3 .momentu oddestylowania dwumetyloiformamidu.Do pozostalosci dodaje- sie eteru etylowego i sa¬ czy. Z przesaczu oddestylowalje sie rozpuszczalnik, a pozostalosc krystalizuje z cykloheksanu.Otrzymuje sie 35,72 czesci walgowych (65,09% wydajnosci teoretycznej) 2,3-dlwuizoibutyrylo-l,2,3,4- -tetrahydriofitailazyny o temperaturze topnienia 103,5—105,5°C.Przyklad IV. Uzywajac 95,35 czesci wago¬ wych jednopotasowej soli l,2-dwu-/trójimetyloa|ce- tylo/-hydrazyny i 52,79 czesci wagowych a,ia'-dwu- bromo-o-lksylenu postepuje sie jak w przykladzie I do momentu oddelstyloiwania diwumeitylofoirmaimi- du. Pozostalosc maderuje sie goraca woda i saczy.Osad przemywa ,sie goraca woda (do momentu gdy widmo IR osadu nie wykazuje obecnosci pasma NH) i suszy.Otrzymuje. sie 34,74 czesci wagowych (57,43% wydajnosci teoinetycznej) 2,3-dwu-/tró,jmet yloiaiciety- lo/-l,z73,'4-tetrahydrot[:talazyny o temperaturze top¬ nienia 178—182°,C. Po krystalizacji z izopropanolu otrzymuje sie 32,16 czesci wagowych (53,17% wy¬ dajnosci teoretycznej) zwiazku topniejacego w tem¬ peraturze 17.9,5'—ll-81,'5°C.Temperatury topnJienlia otrzymanych zwiazków oznaczono na miikiroapairadie Bóetius, a ich budo- 5 we potwierdzono analiza elementarna, widmowa w podczerwieni i spektrografia nnalsowa.Zastrzezenie patentowe 10 Sposób otrzymywania nowych 2,3-dwuaicylowylch pochodnych 1,2,3,4-tetmlhydroftalazy.ny o wzorze ogólnym przedstawionym na rysunku, w którym R oznacza grupe metylowa, izoprojpylowa lub tert.- -butylowa, znamienny tym, ze jednopoitasowe sole 15 1,2-dwuacylohydrazyn poddaje sie reakcji konden¬ sacji z a^-dwuchlorowioo-o^ksylenaimi korzystnie jednopotasowej soli 1,2-dwuacetylohydrazyny z a,a'KlwubromoKHksylenem, przy czym reakcje pro¬ wadzi sie w srodowisku dwumetylofonmainidu, po- 20 czatkowo w temperaturze 20—80°C, korzystnie w temperaturze 60°C, a , nastepnie w temperaturze wrzenia roztworu.N-CO-R N-CO-R DN-3, zain. 424/81 Cena 45 zl PLThe subject of the invention is the method of obtaining new 2,3-bisicyl 1,2,3,4-tetrahyldirophthailazine derivatives of the general formula shown in the figure, in which R represents a methyl, isoiprolpyl or tert.-butyl group. was used for the synthesis of 1,2,3,4-tetrahyd'roiphtalaizin hydrochloride, which is used as a reagent for the determination of formaldehyde and as an intermediate product for the production of compounds with a specific effect, especially on the renal system and the cleavage pathway. The compounds of the general formula shown in the figure are obtained by condensation of the iidinopotasiol salts of 1,2-dipicylohydrasins with a% dihalo-o-xylenes, preferably monopotassium-1,2-diacetylhydlraizine salts, and (kisy] ielnelm, in the environment of dimethylformalmide initially at 20-80 ° C, then at 60 ° C, and then at the boiling point of the solution. The following examples explain the method in more detail It is a long time of the invention. Example 1. 61.68 parts by weight of 1,2-diacetylhydroxy monoptassium salt, times the number of 1000 volumetric parts of dimethyl foaming film, is heated to 60 ° C and is dripped at this temperature for 3 hours at With continuous stirring, a solution of α, α-dibromo-o-xylene 52.79 parts by weight in 500 parts by weight of divumethylfortmaimide was prepared beforehand. After the crawling process, it is heated at the humidity for 3 / hours. From the cooled mixture, the separated piotais bromide is sucked off and from the primrose, dimethylformalmide is distilled off under reduced pressure. The remainder is marooned with water and drained. The precipitate is washed with water (until the IR spectrum of oie shows the presence of paisima NH) and dry. It is estimated at 32.31 parts by weight (74.02% of theoretical yield) 2,3-divuaGetyl-l,! 2.3 , 4-t'etrahydinophthalazine with a melting point of 149-133 ° C. After crystallization, z. of isopripanjol, 30.50 parts by weight (69.87% of theoretical yield) of a compound melting at a temperature of 1511.5-15.2 ° C are obtained, exemplified by example II. Using 61.68 parts by weight of one pot) of the salt of 1,2H, two | cetldhydrirazine and 35.01 parts by weight of a, a'-and -dhchloro-o-clsyliene are semi-dissociated as described in example I. After crystallization from isopropainol, 28, 22 weight parts (64.65 ° C of theoretical output) 2,3-diatoethyl-yl, 2,3,4-tetrahydro phthalaizine, mp 151.5 — U52 ° C. Example III. Using 84.13 parts by weight of a single pot salt of 1,2-diisolbutyrylhydrazine and 52.79 parts by weight of a, "- diblro (mjO-o-xylene is done as in pyramidal I to 111 601111 601 3. The distillation of dimethyl formamide. Diethyl ether and sauces are added to the residue. The solvent has been distilled from the filtrate, and the residue crystallizes from cyclohexane. 35.72 cylinder parts (65.09% of theoretical yield) 2,3-dibutyryl-1 are obtained, 2,3,4-tetrahydrofitailazine with a melting point of 103.5-105.5 ° C. EXAMPLE IV Using 95.35 parts by weight of monopotassium salt of 1,2-di- (trimethyla | cetyl) hydrazine and 52.79 parts by weight of a, and a'-di-bromo-o-lxylene is followed as in example I until the distillation of diwumeitylfoirmaimide. The remainder is made hot water and drained. The sediment is washed, with hot water (until the IR spectrum is removed). the precipitate shows no NH band) and dries. 34.74 parts by weight (57.43% of theoinetic) 2,3-di (triethyl) ethylthyl) -1,3,3,4-tetrahydroth [: talazine, mp 178-182 ° C. After crystallization from isopropanol, 32.16 parts by weight (53.17% of theoretical yield) of a compound melting at a temperature of 17.9.5-1.81.5 ° C are obtained. The melting points of the compounds obtained were determined on the Miikiroapairadie Bóetius, and their structure was confirmed by elemental infrared spectral analysis and nnals spectrography. Patent claim 10 A method of obtaining new 2,3-dipicylic derivatives of 1,2,3,4-tetmlhydrophthalase with the general formula shown in the figure, where R denotes a methyl, isopropyl or tert-butyl group, characterized in that the mono-potassium salts of 1,2-diacylhydrazines are subjected to a condensation reaction with the β-diacetyl-xylenes, preferably the mono potassium 1,2-diacetylhydrazine salt, and ClvubromoKHxylene, the reactions being carried out in the environment of dimethylphonamainide, initially at 20-80 ° C, preferably at 60 ° C, and then at the boiling point of the solution. N-CO-R N-CO-R DN-3, in. 424/81 Price PLN 45 PL

Claims (1)

1. Zastrzezenie patentowe 10 Sposób otrzymywania nowych 2,3-dwuaicylowylch pochodnych 1,2,3,4-tetmlhydroftalazy.ny o wzorze ogólnym przedstawionym na rysunku, w którym R oznacza grupe metylowa, izoprojpylowa lub tert.- -butylowa, znamienny tym, ze jednopoitasowe sole 15 1,2-dwuacylohydrazyn poddaje sie reakcji konden¬ sacji z a^-dwuchlorowioo-o^ksylenaimi korzystnie jednopotasowej soli 1,2-dwuacetylohydrazyny z a,a'KlwubromoKHksylenem, przy czym reakcje pro¬ wadzi sie w srodowisku dwumetylofonmainidu, po- 20 czatkowo w temperaturze 20—80°C, korzystnie w temperaturze 60°C, a , nastepnie w temperaturze wrzenia roztworu. N-CO-R N-CO-R DN-3, zain. 424/81 Cena 45 zl PL1. Claim 10 A method for the preparation of new 2,3-dipicylicyl 1,2,3,4-tetmlhydrophthalase derivatives of the general formula shown in the figure, in which R represents a methyl, isopropyl or tert-butyl group, characterized by that monopoitas salts of 1,2-diacylhydrazines are subjected to the condensation reaction with the di-chloro-o-xylene, preferably with the mono potassium salt of 1,2-diacetylhydrazine, and the reaction taking place in the environment of dimethylphonidine Mimically at a temperature of 20-80 ° C, preferably at a temperature of 60 ° C and then at the boiling point of the solution. N-CO-R N-CO-R DN-3, in. 424/81 Price PLN 45 PL
PL20356577A 1977-12-29 1977-12-29 Process for preparing novel 2,3-diacyl derivatives of 1,2,3,4-tetrahydrophthalazine PL111601B1 (en)

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