CS258638B1 - 3-Acetyl-4-hydroxycarbanilic acid alkyl esters and their preparation - Google Patents

3-Acetyl-4-hydroxycarbanilic acid alkyl esters and their preparation Download PDF

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CS258638B1
CS258638B1 CS869795A CS979586A CS258638B1 CS 258638 B1 CS258638 B1 CS 258638B1 CS 869795 A CS869795 A CS 869795A CS 979586 A CS979586 A CS 979586A CS 258638 B1 CS258638 B1 CS 258638B1
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acid
acetyl
formula
hydroxycarbanilic
alkyl
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CS869795A
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CS979586A1 (en
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Jozef Csoellei
Alois Borovansky
Ludek Benes
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Jozef Csoellei
Alois Borovansky
Ludek Benes
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Abstract

Riešenie sa týká nových alkylesterov kyseliny 3-acetyl-4-hydroxykarbanilovej všeobecného vzorca I, v ktorom R je alkyl s 3 a 4 atómami uhlíka ako i sposobu výroby týchto látok, a to: reakciou 5-amíno-2-hydroxyacetofenónu s alkylesterom kyseliny chlórmravčej v .prostředí organického rozpúšťadla, s výhodou acetonu, alebo Friedel-Craftsovou acyláciou alkylesteru kyseliny 4-hydroxykarbanilovej v prostředí nitrobenzénu pri teplote 105 až 115 °C. Zlúčeniny tohto typu sa móžu využiť ako východiskové suroviny pre přípravu biologicky aktívnych látokThe solution concerns new alkyl esters of 3-acetyl-4-hydroxycarbanilic acid of the general formula I, in which R is alkyl with 3 and 4 carbon atoms, as well as the method of production of these substances, namely: the reaction of 5-amino-2-hydroxyacetophenone with an alkyl ester of chloroformic acid in an organic solvent, preferably acetone, or Friedel-Crafts acylation of the alkyl ester of the acid of 4-hydroxycarbanyl in nitrobenzene at a temperature of 105 to 115 °C. Compounds of this type can be used as starting raw materials for the preparation of biologically active substances

Description

Vynález sa týká alkylesterov kyseliny 3 -acetyl-4-hydroxykarbahilovej všeobecného vzorca IThe invention relates to alkyl esters of 3-acetyl-4-hydroxycarbahilic acid of the general formula I

OHOH

NHCOOR (!) kde R je alkyl s 3 a 4 atómami uhlíka, ako i spósobu přípravy týchto látok.NHCOOR (I) wherein R is alkyl of 3 and 4 carbon atoms, as well as a process for preparing these compounds.

Látky všeobecného vzorca I sú deriváty kyseliny karbanilovej, ktoré sú východiskové suroviny pri přípravě látok s biologickými vlastnosťami (lokálně anestetické, betaadrenolytické a pod.).The compounds of the formula I are carbanilic acid derivatives which are the starting materials in the preparation of substances with biological properties (locally anesthetic, beta-adrenolytic and the like).

Alkylestery kyseliny karbanilovej všeobecného vzorca I je možné podlá vynálezu připravit’ róznymi spósobmi napr. tak, že sa nechá reagovat:The alkyl esters of the carbanilic acid of the formula I can be prepared according to the invention in various ways, e.g. by reacting:

a) 5-amíno-2-hydroxyacetofenón připravený podl'a literatúry (Kunckell F.: Ber. 34, 124 [1901]) s alkylesterom kyseliny chlórmravčej všeobecného vzorca IIa) 5-amino-2-hydroxyacetophenone prepared according to literature (Kunckell F .: Ber. 34, 124 [1901]) with an alkyl chloroformate of formula II

ROCOC1 (II), v ktorom R znamená to isté ako vo vzorci I,ROCOC1 (II) in which R is the same as in formula I,

b) alkylester kyseliny 4-hydroxykarbanilovej všeobecného vzorca III, připravený podlá literatúry (Chabrier P. a spol.: Bull. Soc. Chim. Fr. 1 353 [1955]), v ktorom R znamená to isté ako vo vzorci I sa acyluje v prostředí nitrobenzénu rovnakou metódou popísanou pre syntézu 3-nitro-6-hydroxyacetofenónu (Joshi S. S. a spol.: J. Amer. Chem. Soc. 76, 4 993 [1954]).b) an alkyl ester of 4-hydroxycarbanilic acid of general formula III, prepared according to the literature (Chabrier P. et al .: Bull. Soc. Chim. Fr. 1353 [1955]), wherein R is the same as in formula I is acylated in nitrobenzene medium by the same method described for the synthesis of 3-nitro-6-hydroxyacetophenone (Joshi SS et al .: J. Amer. Chem. Soc. 76, 4 993 [1954]).

OHOH

( lil!(lil!

Bližšie podrobnosti o spósobe výroby látok vyplynú z nasledujúcich príkladov prevedenia, ktoré však rozsah vynálezu neobmedzujú.Further details of the method of manufacture of the materials will be apparent from the following non-limiting examples.

PříkladExample

15,1 g (0,1 mólu) 5-amíno-2-hydroxyacetofenónu sa rozpustí v 150 ml acetónu, přidá sa 7,9 g (0,1 mólu) pyridinu ak vzniknutému roztoku sa postupné přidá za miešania 12,2 g (0,1 mólu) projjylesteru kyseliny chlórmravčej v 30 ml acetónu a zahrieva 1 h. na vodnom kúpeli. Po oddestilování acetónu sa reakčná zmes rozpustí v éteri a pretrepe 15 % roztokom kyseliny chlórovodíkovej. Organická fáza sa vysuší bezvodým uhličitanom sodným a po oddestilovaní éteru sa surový produkt prekryštalizuje z 70 % etanolu. Propylester kyseliny 3-acetyl-4-hydroxykarbanilovej je bielá kryštalická látka, vzniká vo výtažku 67 % teorie, t. t. 72 až 74 °C.Dissolve 15.1 g (0.1 mole) of 5-amino-2-hydroxyacetophenone in 150 ml of acetone, add 7.9 g (0.1 mole) of pyridine and gradually add 12.2 g ( 0.1 mol) of chloroformate in 30 ml of acetone and heated for 1 h. on a water bath. After distilling off the acetone, the reaction mixture was dissolved in ether and shaken with a 15% hydrochloric acid solution. The organic phase is dried over anhydrous sodium carbonate and, after distillation of the ether, the crude product is recrystallized from 70% ethanol. 3-Acetyl-4-hydroxycarbanilic acid propyl ester is a white crystalline solid; t. Mp 72-74 ° C.

Elemen. anal. pre C12H15NO4:Elemen. anal. for C12H15NO4:

Vyp./náj.Vyp./náj.

C 60,75/60,43C 60.75 / 60.43

H 6,36/6,37H, 6.36 / 6.37

N 5,90/5,60N 5.90 / 5.60

IČ — spektrálné charakteristiky: υ (N—H) 3 410 cm-1, v (C=O) 1 728, 1645 cm1, v (C—O—C) 1200 cm-1.IR spectral characteristics: υ (N-H) 3410 cm -1 , v (C = O) 1728, 1645 cm -1 , v (C-O-C) 1200 cm -1 .

Příklad 2Example 2

K roztoku 20,9 g (0,1 mólu) butylesteru kyseliny 4-hydroxykarbanilovej a 15,0 g (0,19 mólu) acetylchloridu v 60 ml nitrobenzénu sa postupné přidá zmes 40 g (0,3 mólu) chloridu hlinitého v 40 ml nitrobenzénu. Reakčná zmes sa nechá 1 h. stát pri teplote mlestnosti a potom sa zahrieva 2 h. pri teplote 105 až 115 °C. Po oddestilování nitrobenzénu s vodnou parou sa surový produkt prekryštalizuje z 50 % metanolu. Butylester kyseliny 3-acetyl-4-hydroxykarbanilovej je bielá kryštalická látka, vzniká vo výtažku 45 % teorie, t. t. 66 až 69 °C.To a solution of 20.9 g (0.1 mol) of 4-hydroxycarbanilic acid butyl ester and 15.0 g (0.19 mol) of acetyl chloride in 60 ml of nitrobenzene are successively added a mixture of 40 g (0.3 mol) of aluminum chloride in 40 ml. nitrobenzene. The reaction mixture is left for 1 h. stand at room temperature and then heat for 2 h. at 105-115 ° C. After distilling off the nitrobenzene with steam, the crude product is recrystallized from 50% methanol. Butyl 3-acetyl-4-hydroxycarbanilic acid ester is a white crystalline solid, yields 45% of theory. t. Mp 66-69 ° C.

Elemen. anal. pre C13H17NO4:Elemen. anal. for C13H17NO4:

Vyp./náj.Vyp./náj.

C 62,13/62,10C 62.13 / 62.10

H 6,82/677H, 6.82 / 677

N 5,57/5,43N 5.57 / 5.43

IČ — spektrálné charakteristiky: v (N—H) 3 416 cm1, v (C=O) 1730, 1650 cm1,IR spectral characteristics: v (N-H) 3416 cm -1 , v (C = O) 1730, 1650 cm -1 ,

1» (C—O—C) 1 205 cm1.1 »(C — O — C) 1 205 cm 1 .

S použitím hoře popísaných metod boli připravené tieto nové v literatúre doposiať nepopísané látky:Using the methods described above, the following novel substances have been prepared in the literature so far:

1. propylester kyseliny 3-acetyl-4-hydroxykarbanilovej, t. t. 72 až 74 °C (etanol—voda) (podl'a příkladu 112)1. 3-acetyl-4-hydroxycarbanilic acid propyl ester, m.p. t. 72-74 ° C (ethanol-water) (according to Example 112)

2. butylester kyseliny 3-acetyl-4-hydroxykarbanilovej, t. t. 66 až 68°C (metanol—voda) (podl'a příkladu 1 i 2).2. 3-acetyl-4-hydroxycarbanilic acid butyl ester, m.p. t. 66-68 ° C (methanol-water) (according to Example 1 and 2).

Claims (4)

1. Alkylestery kyseliny 3-acetyl-4-hydroxykarbanilovej všeobecného vzorca ICLAIMS 1. 3-Acetyl-4-hydroxycarbanilic acid alkyl esters of the general formula I OH i“’ iOH '' i NHCOOR | íf) J kde R je alkyl s 3 a 4 atómami uhlíka.NHCOOR | (f) J wherein R is alkyl of 3 and 4 carbon atoms. 2. Spósob přípravy alkylesterov kyseliny2. A process for preparing alkyl esters of an acid 3-acetyl-4-hydroxykarbanilovej všeobecného vzorca I, podlá bodu 1, vyznačujúci sa tým, že sa nechá reagovat 5-amíno-2-hydroxyacetofenón s alkylesterom kyseliny chlórmravčej všeobecného vzorca II3-Acetyl-4-hydroxycarbanilic acid of the formula I according to claim 1, characterized in that 5-amino-2-hydroxyacetophenone is reacted with an alkyl chloroformate of the formula II ROCOC1 (II),ROCOC1 (II) VYNALEZU kde R znamená to isté ako vo vzorci I, v prostředí organického rozpúšťadla.Where R is the same as in Formula I, in an organic solvent environment. 3. Spósob přípravy pódia bodu 2, vyznačujúci sa tým, že organickým rozpúšťadlom je aceton, diethyléter, metyletylketón alebo petroléter.3. A process according to claim 2, wherein the organic solvent is acetone, diethyl ether, methyl ethyl ketone or petroleum ether. 4. Spósob přípravy alkylesterov kyseliny4. A process for preparing alkyl esters of an acid 3-acetyl-4-hydroxykarbanilovej všeobecného vzorca I, podlá bodu 1, vyznačujúci sa tým, že sa acyluje alkylester kyseliny 4-hydroxykarbánilovej všeobecného vzorca III3-Acetyl-4-hydroxycarbanilic acid of the formula I according to claim 1, characterized in that the 4-hydroxycarbanilic acid alkyl ester of the general formula III is acylated. OHOH NHCOOR ( II I v přítomnosti Friedel-Crafsovho katalyzátorů, kde R znamená to isté ako vo vzorci I v prostředí nitrobenzénu pri teplote 105 až 115 °C.NHCOOR (II I in the presence of Friedel-Crafs catalysts, wherein R is the same as in formula I in nitrobenzene at a temperature of 105 to 115 ° C.
CS869795A 1986-12-22 1986-12-22 3-Acetyl-4-hydroxycarbanilic acid alkyl esters and their preparation CS258638B1 (en)

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