CS233448B1

CS233448B1 - 5-Nitro-2-furyl acetic acid ethyl ester and its method of preparation

Info

Publication number: CS233448B1
Application number: CS828983A
Authority: CS
Inventors: Daniel Vegh; Jaroslav Kovac
Original assignee: Daniel Vegh; Jaroslav Kovac
Priority date: 1983-09-10
Filing date: 1983-09-10
Publication date: 1985-03-14

Abstract

Vynález sa týká antibakteriálneho etylesteru 5-nitro-2-furyloctovej kyseliny, perspektívnej komponenty pre přípravu nových antibiotik. Spfisob přípravy etylesteru kyseliny 5-nitro-2-furyloctovej vzorca je vyznačený tým, že 5-nitro-2-furylvinylidénchlorid, resp. bromid vzorca kde X je Cl a Br reagujú s etanolátmi alkalických kovov vzorca kde M je Li, Na, K v prostředí organických rozpúSťadieí ako benzén, toluén, nitrobenzén, dietyléter, 1,2-dimetoxyetán, tetrahydrofurán, dioxán, octan etylový, etanol a vo vodě alebo v ich zmesiach v rozmedzí teplfit -10 °C až 120 °C.The invention relates to antibacterial ethyl ester of 5-nitro-2-furylacetic acid, a perspective component for the preparation of new antibiotics. The method of preparation of ethyl ester of 5-nitro-2-furylacetic acid is characterized in that 5-nitro-2-furylacetic acid chloride or bromide of the formula where X is Cl and Br react with alkali metal ethanolates of the formula where M is Li, Na, K in the environment of organic solvents such as benzene, toluene, nitrobenzene, diethyl ether, 1,2-dimethoxyethane, tetrahydrofuran, dioxane, ethyl acetate, ethanol and in water or in their mixtures in the temperature range of -10 °C to 120 °C.

Description

Podstata spdsobu přípravy etylesteru 5-nitro-2-furyloctovej kyseliny podTa Vynálezu spočívá v tom, že 5-nitro-2-furylvinylldéndiehlorid, resp.,dibrooid, reagujú s etanolátom sodným, etanolom v prostředí organických rozpúšťadiel, ako'sú aromatická kvapalná uhlovodíky ako benzén, toluén, nitrobenzén v éterech ako dietyléter, 1,2-dimetoxyetén, tetrahydrofurán, dioxán v octane etylovom, etanole vo vodě alebo v ich zmesiach v rozmedzí teplOt -10 až 120 °C.SUMMARY OF THE INVENTION The present invention provides that 5-nitro-2-furyl-vinylidene dihydrochloride or dibrooid is reacted with sodium ethanolate, ethanol in an environment of organic solvents, such as aromatic liquid hydrocarbons. benzene, toluene, nitrobenzene in ethers such as diethyl ether, 1,2-dimethoxyethene, tetrahydrofuran, dioxane in ethyl acetate, ethanol in water or mixtures thereof in the range of -10 to 120 ° C.

zfrom

-CH=cf ♦ CH (II) (III) (I) kde X = Cl, Br a M = Li, Na, Κ, H-CH = cf ♦ CH (II) (III) (I) where X = Cl, Br and M = Li, Na, Κ, H

Etylester 5-nitro-2-furyloctovej kyseliny vykazuje anťibakteriálnu aktivitu voči Gram-pozltívnym ako aj Gram-negatívnym bakteriém. Biologická aktivita uvedených látok sa testovala metodou antimikrobiálneho screeningu, ktorý pozostával z antimikrobiálneho, antifungálneho a antiprotozoálneho screeningu. Antibakteriálny a antiprotozoálny screening sa prevádzal na nasledujúce kmene: Staphylococcus CCM 885; Bacillus subtilis CCU 2216; Escherichia coli CCM 5172; Pseudomonas aeruginosa CCM 1960; Aspergillus niger P 300; Candida pseudotropicalis a Euglena gracilis kmeň Z z Haskins Laboratories at Peace University N. Y. USA. V testovaných koncentráciach 3,125; 12,5; 50 yum/dlsk vykazovala'látka na všetky mikroorganizmy inhibičnú aktivitu.5-Nitro-2-furyl acetic acid ethyl ester exhibits antibacterial activity against both Gram-positive and Gram-negative bacteria. The biological activity of the compounds was tested by an antimicrobial screening method consisting of antimicrobial, antifungal and antiprotozoal screening. Antibacterial and antiprotozoal screening was performed on the following strains: Staphylococcus CCM 885; Bacillus subtilis CCU 2216; Escherichia coli CCM 5172; Pseudomonas aeruginosa CCM 1960; Aspergillus niger P 300; Candida pseudotropicalis and Euglena gracilis strain Z of Haskins Laboratories at Peace University N.Y. USA. At tested concentrations of 3.125; 12.5; 50 µm / dl exhibited inhibitory activity on all microorganisms.

Pozornost věnovaná tejto látke stimuluje perspektivné možné využitie pre přípravu nových antibiotik penieilínového a cefalosporínového radu s 5-nitro-2-furyloyým zvyškom.Attention to this substance stimulates the prospective use for the preparation of novel antibiotics of the penieillin and cephalosporin series with the 5-nitro-2-furyloy residue.

Predmet ilustrujú, ale neobmedzujú nasledujúce příklady.The subject matter is illustrated but not limited by the following examples.

Příklad 1 g hydroxidu sodného sa rozpustilo v 200 ml 95# etanole a pri 10 °C sa zlialo s 2,1 g 5-nitro-2-furylvinyléndichlorldu v 50 ml 95% etanole. Po 10 min intenzívneho miešania teplota sa zvýši na 50 °C. Po 50 min sa reakčné zmes znovu schladí na 10 °C a za intenzívneho miešania prileje sa 5,5 ml kyseliny octovej. Hozpúšťadlo sa oddestiluje za vákua a zvyšok sa čistí ohromatografický na stípci silikagelu (150 až 250 mesh). Získá sa 1,45 g etylesteru 5-nitro-2-furyloctovej kyseliny o t. t. 51 až 53 °C.Example 1 g of sodium hydroxide was dissolved in 200 ml of 95% ethanol and at 10 ° C was poured into 2.1 g of 5-nitro-2-furylvinylenedichloride in 50 ml of 95% ethanol. After 10 minutes of vigorous stirring, the temperature was raised to 50 ° C. After 50 min, the reaction mixture was recooled to 10 ° C and 5.5 ml of acetic acid was added with vigorous stirring. The solvent was distilled off under vacuum and the residue was purified by chromatography on a silica gel (150-250 mesh) column. 1.45 g of 5-nitro-2-furylacetic acid ethyl ester of m.p. t. Mp 51-53 ° C.

Sumárny vzorec zlúčeniny CgH^NO^. Molekulová hmotnost 199,1.The general formula of C 8 H 11 NO 2. Molecular Weight 199,1.

Teplota topenia 51 až 53 °C.Mp 51-53 ° C.

Vypočítané: 48,20 % C; 4,55 % H; 7,03 % NCalculated: C, 48.20; 4.55% H; N, 7.03

Nájdené: 47,87 % C; 4,47 % H; 6,83 % N.Found: C, 47.87; 4.47% H; 6.83% N.

¹H NMR spektrum sa meralo na spektrometr! TESLA’BS v CDCl^ za použitia interného Standardu tetrametylsilánu. ^{The 1} H NMR spectrum was measured on a spectrometer. TESLA'BS in CDCl 3 using an internal standard of tetramethylsilane.

8H^ 7,28 ppm; δΗ^ = 6,55 ppm; J_{H H} = 3,9 Hz; 8CH₂8CH₃ = 1 ,28 ppm ³⁴ ΔH δ 7.28 ppm; δΗ ^ = 6.55 ppm; J _{H H} = 3.9 Hz; 8CH ₂ 8CH ₃ = 1.28 ppm ³⁴

3,81 ppm; ROCHg = 4,23 ppm;3.81 ppm; ROCH 8 = 4.23 ppm;

Příklad 2 .Example 2.

g 5-nitro-2-furylvinylidéndichloridu sa rozpustilo v ,00 ml benzénu a za intenzivneho miešania pri teplote 50 °C sa přidalo k 20 g hydrojddu sodného v 1 000 ml 95« etanolu. Po 10 min sa reakčná zmes neutralizovala s 14 ml kyseliny octovej a rozpúštadlo sa oddeStilovalo do sucha. Pri zriedení zvyšku s 200 ml vody organická látka sa extrahovala do éteru a po odpařeni éteru sa čistila analogicky ako v přiklade 1. Ziska sa 5 g etylesterů 5-nitro-2-furyloctovej kyseliny o t. t. 51 °C.5 g of 5-nitro-2-furylvinylidene dichloride was dissolved in 100 ml of benzene and added, with vigorous stirring at 50 ° C, to 20 g of sodium hydroiodide in 1000 ml of 95% ethanol. After 10 min, the reaction mixture was neutralized with 14 mL of acetic acid and the solvent was distilled off to dryness. On dilution of the residue with 200 ml of water, the organic substance was extracted into ether and, after evaporation of the ether, purified in analogy to Example 1. 5 g of 5-nitro-2-furylacetic acid ethyl esters were obtained, m.p. t. Deň: 32 ° C.

P r i k 1 a d 3 g 5-nitro-2-furylvinylldéndibromidu v 50 ml 95« etanole sa přidá k 3 g hydroxidu draselného v 150 ml etanole pri 50 °C a po 1 h sa reakčná zmes zahusti za vákua. Po přidaní 50 ml vody organická látka sa extrahuje do éteru. Po odpaření éteru zvyšok sa čistí analogicky ako v příklade 1. Získá sa 1 g etylesterů 5-nitro-2-furyloctovej kyseliny o t. t. 5, °C.EXAMPLE 3 3 g of 5-nitro-2-furylvinylldenedibromide in 50 ml of 95% ethanol are added to 3 g of potassium hydroxide in 150 ml of ethanol at 50 DEG C. and after 1 h the reaction mixture is concentrated in vacuo. After addition of 50 ml of water, the organic matter is extracted into ether. After evaporation of the ether, the residue is purified analogously to Example 1. 1 g of 5-nitro-2-furylacetic acid ethyl esters of m.p. t. 5 ° C.

Claims

OBJECT OF THE INVENTION

1. 5-Nitro-2-furylacetic acid ethyl ester of the formula I ch ₂ -cooch ₂ ch ₃ (I)

2. A process for the preparation of 5-nitro-2-furylootic acid ethyl esters by reacting 5-nitro-2-furylvinylidene dichloride or dibromide of the general formula II as defined in formula II by ₂ n (II) wherein X is Cl or Br. alkali metals of formula ch ₃ ch ₂ om (III) *

where M is Li, Na, K, in an environment of organic solvents from the group of aromatic liquid hydrocarbons such as benzene, toluene, nitrobenzene, ethers such as diethyl ether, 1,2-dimethoxyethane, tetrahydrofuran, dioxane, ethyl acetate, ethanol in water or mixtures thereof in the range of -10 ° C to 120 ° C.