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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- Czechoslovakia
- Prior art keywords
- narceonic
- acid
- benzyl
- ethenyl
- compounds derived
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims description 10
- 239000002253 acid Substances 0.000 title claims description 8
- 238000004519 manufacturing process Methods 0.000 title 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- -1 Benzyl-3,4-dihydro-5,6-dimethoxyphthalazine Chemical compound 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 239000011541 reaction mixture Substances 0.000 claims description 3
- 238000009835 boiling Methods 0.000 claims 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000000463 material Substances 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- JUCCMEHWBGPJKS-UHFFFAOYSA-N 4-benzyl-2h-phthalazin-1-one Chemical compound C12=CC=CC=C2C(=O)NN=C1CC1=CC=CC=C1 JUCCMEHWBGPJKS-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- VSTDWFOKFHOUPO-UHFFFAOYSA-N C1=NN=CC=2C(CC=CC12)=O Chemical compound C1=NN=CC=2C(CC=CC12)=O VSTDWFOKFHOUPO-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 150000002429 hydrazines Chemical class 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- YRTPZXMEBGTPLM-UVTDQMKNSA-N (3z)-3-benzylidene-2-benzofuran-1-one Chemical compound C12=CC=CC=C2C(=O)O\C1=C/C1=CC=CC=C1 YRTPZXMEBGTPLM-UVTDQMKNSA-N 0.000 description 1
- ZDQCLDBVVQUHDH-UHFFFAOYSA-N 6h-isoquinolin-5-one Chemical compound N1=CC=C2C(=O)CC=CC2=C1 ZDQCLDBVVQUHDH-UHFFFAOYSA-N 0.000 description 1
- DEXMFYZAHXMZNM-UHFFFAOYSA-N Narceine Chemical class OC(=O)C1=C(OC)C(OC)=CC=C1C(=O)CC1=C(CCN(C)C)C=C(OCO2)C2=C1OC DEXMFYZAHXMZNM-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000003934 aromatic aldehydes Chemical class 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical class C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Landscapes
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
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.
Claims (3)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS234979A CS203756B1 (en) | 1979-04-06 | 1979-04-06 | Tetracyclic compounds derived from narceonic acid and process for preparing thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS234979A CS203756B1 (en) | 1979-04-06 | 1979-04-06 | Tetracyclic compounds derived from narceonic acid and process for preparing thereof |
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| Publication Number | Publication Date |
|---|---|
| CS203756B1 true CS203756B1 (en) | 1981-03-31 |
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| Application Number | Title | Priority Date | Filing Date |
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| CS234979A CS203756B1 (en) | 1979-04-06 | 1979-04-06 | Tetracyclic compounds derived from narceonic acid and process for preparing thereof |
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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 |
-
1979
- 1979-04-06 CS CS234979A patent/CS203756B1/en unknown
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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