CS276922B6 - 3-Aidomethyl-4-hydroxyphenylalkylthetones and their preparation - Google Patents

3-Aidomethyl-4-hydroxyphenylalkylthetones and their preparation Download PDF

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Publication number
CS276922B6
CS276922B6 CS6990A CS6990A CS276922B6 CS 276922 B6 CS276922 B6 CS 276922B6 CS 6990 A CS6990 A CS 6990A CS 6990 A CS6990 A CS 6990A CS 276922 B6 CS276922 B6 CS 276922B6
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Czechoslovakia
Prior art keywords
preparation
azidomethyl
ketones
general formula
hydroxyphenylalkyl
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CS6990A
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Czech (cs)
Slovak (sk)
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CS9000069A2 (en
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Ruzena Rndr Csc Cizmarikova
Eva Rndr Csc Misikova
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Univ Komenskeho
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Publication of CS276922B6 publication Critical patent/CS276922B6/en

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  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Riešenie sa týká nových 3-azidometyl- -4-hydroxyfenylalkylketónov všeobecného vzorca I, kde R je metyl a etyl. Spósob ich pripravy spočívá v tom, že na 4-hydroxy-3-chlórmetylfenylalkylketóny sa pósobí azidom sodným v dimetylformamide pri teplote 30 °C počas 24 hodin. Připravené nové 3-azidometyl-4-hydroxyfenvlalkylketóny všeobecného vzorca I móžu byt použité ako medziprodukty pre přípravu primárných amínov resp. solí, z ktorých je možné připravit nové látky s biologickou aktivitou.The solution relates to new 3-azidomethyl-4-hydroxyphenylalkyl ketones of the general formula I, where R is methyl and ethyl. The method of their preparation consists in treating 4-hydroxy-3-chloromethylphenylalkyl ketones with sodium azide in dimethylformamide at a temperature of 30 °C for 24 hours. The prepared new 3-azidomethyl-4-hydroxyphenylalkyl ketones of the general formula I can be used as intermediates for the preparation of primary amines or salts, from which it is possible to prepare new substances with biological activity.

Description

1 CS 276922 B6

Vynález sa týká nových 3-azidometyl-4-hydroxyfenylalkyl-ketónov všeobecného vzorca

kde R je metyl a etyl a spósobu ich přípravy.

Na základe literárnej rešerše ako i patentovej literatúrylátky uvedené pod všeobecným vzorcom I sú originálně doterazv literatúre nepopísané. Ide o deriváty p-hydroxyacetofenólua p-hydroxypropiofenólu, z ktorých mnohé vykazujú antibakteriál-nu, lokálnoanestetickú a antiarytmickú, beta-adrenolytickú akti-vitu. Připravené nové azidy všeobecného vzorca I móžu by£ použitéako medziprodukty pre přípravu primárných amínov resp. ich solí,z ktorých je možné připravit nové látky s biologickou aktivitu.

Spósob přípravy uvedených látok I spočívá v tom, že na4-hydroxy-3-chlórmetylfenylalkylketón připravený podlá SohdaS. a kol. J.Med.Chem. 22,279 /1979/ pósobí azidom sodným v dime-tylformamide pri teplote 30 °C. . Podrobnosti přípravy sú uvedené v nasledujúcom příklade. 3-az idomety1-4-hydroxyfenylmetylketón 0,lmol 4-hydroxy-3-chlórmetylfenylmetylketón sme rozpustili v 20ml bezvodého dimetylformamidu a po častiach sme přidali 0,1 molazidu sodného v 55 ml bezvodého dimetylformamidu tak, aby teplotareakčnej zmesi neprestúpila 30 °C. Potom sa reakčná zmes miešala24 hodin pri teplote miestnosti. Vylúčený chlorid sodný sa odfil-troval a dimetyiformamid sa volné odpařil na hodinových sklíč-kách. Získaná biela kryštalická látka sa přečistila kryštalizáci-ou z etylacetátu. Výtažok 60 %. Teplota topenia 140 až 143 °C/nekorigovaná/

Analýza pre CqH9N3O2 /Mr. = 191,18 /vypočítaná % C =56,54.,% H = 4,74., % N = 21,97., zistené % C = 56,24., % H = 4,85.,% N = 21,72.

Infračeprené spektrum /nujol/V /C=C/ 1584 cm”1., /0=0/1666 cm“1.,V /N-,/ = 2088 /dva alebo rozlišené pásy/., y /OH/ =3 200 - 3 500 cm T.

Ultrafialové spektrum /metanol/ λmax = 228 nm /log^* = 3,71/272 nm /logf = 3,73/.

1H-NMR

ch2-N

1 CS 276922 B6

The present invention relates to novel 3-azidomethyl-4-hydroxyphenylalkyl ketones of the general formula

wherein R is methyl and ethyl and a method for their preparation.

Based on the literature search as well as the patent literature, the compounds of formula (I) have not been previously described in the literature. These are p-hydroxyacetophenol and p-hydroxypropiophenol derivatives, many of which exhibit antibacterial, local anesthetic and antiarrhythmic, beta-adrenolytic activity. The prepared novel azides of the formula I can be used as intermediates for the preparation of primary amines, respectively. salts thereof, from which new substances with biological activity can be prepared.

The method of preparing said compounds I is that the 4-hydroxy-3-chloromethylphenylalkyl ketone prepared according to SohdaS. et al. J.Med.Chem. 22,279 (1979) with sodium azide in dimethylformamide at 30 ° C. . Details of the preparation are given in the following example. 3-azomethyl-4-hydroxyphenylmethyl ketone 0.1mol 4-Hydroxy-3-chloromethylphenylmethylketone was dissolved in 20mL of anhydrous dimethylformamide and 0.1mol of sodium sodium molazide in 55mL of anhydrous dimethylformamide was added portionwise to avoid a temperature of 30 ° C. Then the reaction mixture was stirred at room temperature for 24 hours. The precipitated sodium chloride was filtered off and the dimethyiformamide was freely evaporated on an hour slide. The white crystalline solid obtained was purified by crystallization from ethyl acetate. Yield 60%. Mp 140-143 ° C (uncorrected)

Analysis for C 10 H 9 N 3 O 2 / Mr. = 191.18 (calculated% C = 56.54,% H = 4.74,% N = 21.97, found% C = 56.24,% H = 4.85,% N = 21.72.

Infrared Spectrum / Nujol / V / C = C / 1584 cm 1, 1/0 = 0/1666 cm 1, V / N -, / = 2088 / two or differentiated bands / y, OH / = 3 200-3,500 cm T.

Ultraviolet Spectrum / Methanol (λ max = 228 nm / log log = 3.71 / 272 nm (logf = 3.73).

1 H-NMR

ch2-N

Claims (2)

CS 276922 B6 2 δ = 2,59 CH3CO /s,3H/., 4,48 ΟΗ,Νο /s,2H/., 6,96 Hg /m,lH/., 7,26 OH /s,lH/., 7,89 H9 /m,2H/l5C-NMR ' δ = 26,36 CH3., 50,75 CH2N3., 116,04 Cg., 122,05 C3., 130,11 C-l·, 130,96,131,08 C2,Cg, 159,29 C4·, 197,13 CO. Týmto postupom bol připravený i 3-azidometyl-4-hydroxyfenyl-etylketón : Teplota topenia 110 až 113 °C Analýza pre ciohhn3°2 /Mr. = 205,22/ vypočítané % C = 58,53., % H = 5,40., % N = 20,48., zistené % C = 58,84., % H = 5,63., % N = 20,75. Infračervené spektrum /nujol/ "V /C=C/ 1954 cm“1., V /C=O/ 1666 cm“1 V /N3/ 2084,2112 cm”1 /dublet/., ý /OH/ 3200-3500 cm“1. Ultrafialové spektrum /metanol/A max = 222 nm /log£ = 4,07/, 271 nm /log £ = 4,14/. PATENTOVÉ NÁROKY 1. 3-azidometyl-4-hydroxyfenylalkylketóny všeobecného vzorca I kde R je metyl a etyl OHΔ = 2.59 CH 3 CO (s), 3 H (4.48), δ (s), 2H (δ), 6.96 (Hg), (1H), 7.26 (OH), s (1H). , 7.89 H9 / m, 2H / 15 C-NMR δ = 26.36 CH 3., 50.75 CH 2 N 3., 116.04 Cg., 122.05 C 3, 130.11 Cl ·, 130.96.131 , 08 C2, Cg, 159.29 C4 ·, 197.13 CO. 3-Azidomethyl-4-hydroxyphenyl-ethyl ketone was prepared by this procedure: mp 110-113 ° C Analysis for c / 2 / Mr. = 205.22 / calculated% C = 58.53.% H = 5.40.% N = 20.48. Found% C = 58.84.% H = 5.63.% N = 20.75. Infrared / nujol / "V / C = C / 1954cm" 1, V / C = 0 / 1666cm "1V / N3 / 2084.2112cm" 1 / doublet /., Ý / OH / 3200-3500 Ultraviolet Spectrum / Methanol (A max = 222 nm / log δ = 4.07), 271 nm (log δ = 4.14) PATENT RIGHTS 1. 3-Azidomethyl-4-hydroxyphenylalkylketones of Formula I wherein R is methyl and ethyl OH CH2N3CH2N3 2. Spósob přípravy 3-azidometyl-4-hydroxyfenylalkylketónov všeo-becného vzorca I, vyznačujúci sa tým, že sa nechájú reagovat4-hydroxy-3-chlórmetylfenylalkylketóny s azidom sodným v pros-tředí dimetylformamidu pri 30 °C počas 24 hodin. Konec dokumentu2. A process for the preparation of 3-azidomethyl-4-hydroxyphenylalkyl ketones of the general formula (I), characterized in that 4-hydroxy-3-chloromethylphenylalkyl ketones with sodium azide are reacted in dimethylformamide at 30 DEG C. for 24 hours. End of document
CS6990A 1990-01-05 1990-01-05 3-Aidomethyl-4-hydroxyphenylalkylthetones and their preparation CS276922B6 (en)

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CS276922B6 true CS276922B6 (en) 1992-09-16

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