CS203756B1 - Tetracyclic compounds derived from narceonic acid and process for preparing thereof - Google Patents
Tetracyclic compounds derived from narceonic acid and process for preparing thereof Download PDFInfo
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- CS203756B1 CS203756B1 CS234979A CS234979A CS203756B1 CS 203756 B1 CS203756 B1 CS 203756B1 CS 234979 A CS234979 A CS 234979A CS 234979 A CS234979 A CS 234979A CS 203756 B1 CS203756 B1 CS 203756B1
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Description
Vynález se týká tetracyklických sloučenin odvozených od kyselin narceonové obecného vzorce I,The invention relates to tetracyclic compounds derived from narceonic acids of the general formula I,
kdewhere
X značí atoni kyslíku nebo seskupení — N—R, ve kterémX denotes an oxygen atom or - N — R group in which
R je atom vodíku, fenyl, popřípadě substituovaný atomem chloru, bromu nebo nitroskupinou.R is hydrogen, phenyl, optionally substituted with chlorine, bromine or nitro.
Sloučeniny obecného vzorce I, které dosud nebyly popsány, jsou farmakologicky cenné látky s potenciálními bakteriostatickými účinky.The compounds of the formula I which have not been described so far are pharmacologically valuable substances with potential bacteriostatic effects.
V blízké oblasti se reakcemi aromatických ketokyselin s deriváty hydražinu, při nichž vznikly deriváty ftalazinu, zabývali například Vaughan a Baird (J. Am. Chem. Soc. 68, 1314, 1946); z benzylidenftalidu reakcí s hydrazinem získal Bromberg (Ber. 29, 1434, 1896) l-benzyl-3,4-dihydroftalazin-4-on; z derivátu narceinu, kyseliny narceinové, připravili Freund a Frankfortér (Ann. 277, 20, 1893) l-(2‘-ethenyl)benzyl-3,4-dihydroftalazin-4-on. Reakcí aromatických aldeihydokyselin s hydroxylaminem sé zabýval například Brady se sp. (J. Chém. Soc. 529, 1928), přičemž syntetizoval deriváty ΙΗ-benzo (d)-(1,2) oxazinu.In the near field, reactions of aromatic keto acids with hydrazine derivatives to produce phthalazine derivatives have been discussed, for example, by Vaughan and Baird (J. Am. Chem. Soc. 68, 1314, 1946); from benzylidene phthalide by treatment with hydrazine gave Bromberg (Ber. 29, 1434, 1896) 1-benzyl-3,4-dihydrophthalazin-4-one; from narcein derivative, narceinic acid, prepared by Freund and Frankfortér (Ann. 277, 20, 1893) 1- (2‘-ethenyl) benzyl-3,4-dihydrophthalazin-4-one. The reaction of aromatic aldehydes with hydroxylamine has been studied, for example, by Brady sp. (J. Chem. Soc. 529, 1928), synthesizing ΙΗ-benzo (d) - (1,2) oxazine derivatives.
Při způsobu výroby tetracyklických sloučenin podle vynálezu uvedeného obecného vzorce se postupuje například tak, že se nejprve z (E)- nebo (Z)-isomeru kyseliny narceonové reakcí s deriváty hydražinu v mírně bazickém prostředí, s výhodou v přítomnosti octanu sodného nebo pyridinu, připraví derivát l-(2‘-ethenyl)benzyl-3,4-dihydroftalazin-4-onu, popřípadě reakcí s hydroxylaminem derivát 4-(2‘-ethenyl)benzyl-lH-benzo-(d)-(l,2)oxazin-l-onu; získané deriváty se potom v kyselém prostředí, s výhodou v methanolickém roztoku chlorovodíku, při teplotě. varu reakční směsi cyklizují na příslušný derivát s požadovaným významem substituentu R.The process for the preparation of the tetracyclic compounds according to the invention of the general formula is carried out, for example, by first preparing the (E) - or (Z) -isomer of narceonic acid by reaction with hydrazine derivatives in a slightly basic medium, preferably in the presence of sodium acetate or pyridine. 1- (2'-ethenyl) benzyl-3,4-dihydrophthalazin-4-one derivative, optionally by reaction with hydroxylamine 4- (2'-ethenyl) benzyl-1H-benzo (d) - (1,2) oxazine derivative -l-one; the derivatives obtained are then acidified, preferably in a methanolic solution of hydrogen chloride, at a temperature. the reaction mixture is cyclized to the corresponding derivative with the desired meaning of substituent R.
.. Bližší podrobnosti vyplývají z příkladů provedení. ,.. Further details are given in the examples. ,
Příklad 1Example 1
Příprava 5,6-dihydro-3,4,12-trimethoxy-8-mgthyl-10,ll-methylendioxy-8H-isochinolo(2,3-'a)ftalazin-5-onu , . .Preparation of 5,6-dihydro-3,4,12-trimethoxy-8-mg-ethyl-10,11-methylenedioxy-8H-isoquinolo (2,3-a) phthalazin-5-one. .
1,0 g kyseliny narceonové se· smíchá s roztokem 4,0 ml hydrazinhydrátu ve 30 ml ethanolu a směs se refluxuje 4 hodiny na vodní lázni. Vyloučené krystaly l-(6‘-ethenyl-2‘-methoxy-3‘,4‘-methylendioxy)benzyl-3,4-dlhydro-5,6-dimethoxyftalazin-4-onu se odsají a překrystalují z ethanolu. Výtěžek 0,32 g, t. t. 276 až 278 °C. 0,20 g této látky se refluxuje 1 hodinu v 50 ml 5% methanolického roztoku chlorovodíku, roztok se zahustí na objem 10 ml, vlije do studené vody, pH se upraví přídavkem 1% roztoku amoniaku na hodnotu 6,9 a roztok se extrahuje .3 X po 10 ml chloroformu. Spojené extrakty se zahustí ke krystalizací a získaná látka se překrýstaluje z methanolu. Výtěžek 0,120 g žádané látky, t. t. 179 až 181 °C.1.0 g of narceonic acid is mixed with a solution of 4.0 ml of hydrazine hydrate in 30 ml of ethanol and the mixture is refluxed for 4 hours on a water bath. The precipitated crystals of 1- (6‘-ethenyl-2‘-methoxy-3‘, 4‘-methylenedioxy) benzyl-3,4-dlhydro-5,6-dimethoxyphthalazin-4-one are filtered off with suction and recrystallized from ethanol. Yield 0.32 g, mp 276-278 ° C. 0.20 g of this material is refluxed for 1 hour in 50 ml of 5% methanolic hydrogen chloride solution, the solution is concentrated to 10 ml, poured into cold water, adjusted to pH 6.9 with 1% ammonia solution and extracted. 3 x 10 ml chloroform. The combined extracts were concentrated to crystallize and the material was recrystallized from methanol. Yield 0.120 g of the desired compound, m.p. 179-181 ° C.
P ř í k 1 a d 2Example 1 a d 2
Příprava 6-fenyl-5,6-dihydro-10,ll-methylendioxy-3,4,12-trimethoxy-8-methyl-8H-isochinolo (2,3-a ] -ftalazin-5-onuPreparation of 6-phenyl-5,6-dihydro-10,11-methylenedioxy-3,4,12-trimethoxy-8-methyl-8H-isoquinolo [2,3-a] phthalazin-5-one
Roztok 0,5 g kyseliny narceonové ve 30 mililitrech ethanolu se refluxuje 4 hodiny s 0,5 g fenylhydrdzinu a 0,5 g octanu sodného. Ochlazením· reakční směsi vyloučená látka se překrýstaluje z ethanolu, čímž se získá 0,36 g l-(6‘-ethenyl-2‘-methoxy-3‘,4‘-methylendioxy) benzyl-3-f enyl-3,4-dihydro-5,6-dimethoxyftalazin-4-ohu s t. t. 185 až 186 “C. 0,18 g této látky se .30 minut refluxuje ve 25 ml 5% methanolického roztoku chlorovodíku. Roztok se zahustí na objem 10 mililitrů a vlije do 50 ml 5% roztoku amoniaku. Vyloučená oranžová látka se odfiltruje, vysuší a překrýstaluje z methanolu. Výtěžek žádané látky je 0,15 g, t. t. 185,5 °C. P ř í k 1 a d 3A solution of 0.5 g of narceonic acid in 30 ml of ethanol is refluxed for 4 hours with 0.5 g of phenylhydrdzine and 0.5 g of sodium acetate. The precipitated material was recrystallized from ethanol to give 0.36 g of 1- (6'-ethenyl-2'-methoxy-3 ', 4'-methylenedioxy) benzyl-3-phenyl-3,4- dihydro-5,6-dimethoxyphthalazin-4-one having mp 185-186 ° C; 0.18 g of this material was refluxed in 25 ml of 5% methanolic hydrogen chloride solution for 30 minutes. The solution is concentrated to a volume of 10 ml and poured into 50 ml of 5% ammonia solution. The resulting orange solid was filtered off, dried and recrystallized from methanol. The yield of the desired compound is 0.15 g, mp 185.5 ° C. Example 1 a d 3
Příprava 5,8-dihydro-3,4,12-trimethoxy-8-methyl-10,ll-methylendioxy-benz(d) (l,2)oxazino (3,4-b)izochinol-5-onuPreparation of 5,8-dihydro-3,4,12-trimethoxy-8-methyl-10,11-methylenedioxybenz (d) (1,2) oxazino (3,4-b) isoquinol-5-one
0,3 g kyseliny narceonové se refluxují s 0,5 g hydrochloridu hydroxylaminu ve směsi 20 ml ethanolu a 5 ml pyridinu po dobu 20 hodin. Ochlazením vyloučené krystaly (0,21 g) se překrystalují z ethanolu. Výtěžek 0,19 g 4-(6‘-ethenyl-3‘,4‘-methylendioxy-2‘-methoxy) benzyl-7,8-dihydro-lH-benzo- . [d] (l,2)oxazin-l-onu s t. t. 196 až 197 °C. 0,18 g této látky se refluxuje 1 hodinu se 70 mililitry 5% methanolického roztoku chlorovodíku.. Roztok se. zahustí a odparek se vlije do 50 ml 10% roztoku amoniaku, vyloučená látka se odfiltruje a překrýstaluje' z ethano, lu. Výtěžek žádané látky je 0,13 g, t. t. 196 až 198 °C.0.3 g of narceonic acid is refluxed with 0.5 g of hydroxylamine hydrochloride in a mixture of 20 ml of ethanol and 5 ml of pyridine for 20 hours. The crystals precipitated (0.21 g) were recrystallized from ethanol. Yield 0.19 g of 4- (6‘-ethenyl-3‘, 4‘-methylenedioxy-2‘-methoxy) benzyl-7,8-dihydro-1H-benzo. [d] (1,2) oxazin-1-one, mp 196-197 ° C. 0.18 g of this material was refluxed for 1 hour with 70 ml of 5% methanolic hydrogen chloride solution. The mixture is concentrated and the residue is poured into 50 ml of 10% ammonia solution, the precipitate is filtered off and recrystallized from ethanol. The yield of the desired compound is 0.13 g, mp 196-198 ° C.
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108794497A (en) * | 2018-07-09 | 2018-11-13 | 江西中医药大学 | A kind of new N- benzyls acridone type alkaloid and preparation method thereof and purposes |
CN115746020A (en) * | 2022-11-10 | 2023-03-07 | 南京林业大学 | Preparation of novel tetra-cyclic compounds without metal |
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1979
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108794497A (en) * | 2018-07-09 | 2018-11-13 | 江西中医药大学 | A kind of new N- benzyls acridone type alkaloid and preparation method thereof and purposes |
CN115746020A (en) * | 2022-11-10 | 2023-03-07 | 南京林业大学 | Preparation of novel tetra-cyclic compounds without metal |
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