ES2245584B2 - PROCEDURE OF ELECTROCHEMICAL HYDROXYLATION FROM MONOCARBOXYL ACIDS OF QUINOLINE OR ITS CARBOXYLATES, TO PRODUCE HYDROXY-QUINOLINES AND QUINOLONES. - Google Patents
PROCEDURE OF ELECTROCHEMICAL HYDROXYLATION FROM MONOCARBOXYL ACIDS OF QUINOLINE OR ITS CARBOXYLATES, TO PRODUCE HYDROXY-QUINOLINES AND QUINOLONES.Info
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- ES2245584B2 ES2245584B2 ES200400306A ES200400306A ES2245584B2 ES 2245584 B2 ES2245584 B2 ES 2245584B2 ES 200400306 A ES200400306 A ES 200400306A ES 200400306 A ES200400306 A ES 200400306A ES 2245584 B2 ES2245584 B2 ES 2245584B2
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- catholyte
- quinolones
- electrochemical
- electrolysis
- quinolines
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- 238000000034 method Methods 0.000 title claims abstract description 17
- 230000033444 hydroxylation Effects 0.000 title claims abstract description 10
- 238000005805 hydroxylation reaction Methods 0.000 title claims abstract description 10
- 150000007942 carboxylates Chemical class 0.000 title claims abstract description 9
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 title claims description 3
- 239000002253 acid Substances 0.000 title claims 3
- FNXKBSAUKFCXIK-UHFFFAOYSA-M sodium;hydrogen carbonate;8-hydroxy-7-iodoquinoline-5-sulfonic acid Chemical compound [Na+].OC([O-])=O.C1=CN=C2C(O)=C(I)C=C(S(O)(=O)=O)C2=C1 FNXKBSAUKFCXIK-UHFFFAOYSA-M 0.000 title abstract description 5
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 title 2
- 150000007513 acids Chemical class 0.000 title 1
- 238000005868 electrolysis reaction Methods 0.000 claims abstract description 13
- 150000001875 compounds Chemical class 0.000 claims abstract description 12
- 150000007660 quinolones Chemical class 0.000 claims abstract description 8
- 239000012528 membrane Substances 0.000 claims abstract description 7
- 239000003792 electrolyte Substances 0.000 claims abstract description 6
- 229910021607 Silver chloride Inorganic materials 0.000 claims abstract description 5
- 239000007864 aqueous solution Substances 0.000 claims abstract description 5
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 claims abstract description 5
- 239000007858 starting material Substances 0.000 claims abstract description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 12
- 239000000243 solution Substances 0.000 claims description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 claims description 6
- 229910002804 graphite Inorganic materials 0.000 claims description 6
- 239000010439 graphite Substances 0.000 claims description 6
- 229910052697 platinum Inorganic materials 0.000 claims description 6
- 229910052719 titanium Inorganic materials 0.000 claims description 6
- 239000010936 titanium Substances 0.000 claims description 6
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 4
- 230000009467 reduction Effects 0.000 claims description 4
- XOLBLPGZBRYERU-UHFFFAOYSA-N tin dioxide Chemical compound O=[Sn]=O XOLBLPGZBRYERU-UHFFFAOYSA-N 0.000 claims description 4
- 239000003575 carbonaceous material Substances 0.000 claims description 3
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 2
- 229910000831 Steel Inorganic materials 0.000 claims description 2
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 2
- 239000000956 alloy Substances 0.000 claims description 2
- 229910045601 alloy Inorganic materials 0.000 claims description 2
- 229910052802 copper Inorganic materials 0.000 claims description 2
- 239000010949 copper Substances 0.000 claims description 2
- 238000009792 diffusion process Methods 0.000 claims description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052737 gold Inorganic materials 0.000 claims description 2
- 239000010931 gold Substances 0.000 claims description 2
- 150000002500 ions Chemical class 0.000 claims description 2
- 229910052742 iron Inorganic materials 0.000 claims description 2
- YADSGOSSYOOKMP-UHFFFAOYSA-N lead dioxide Inorganic materials O=[Pb]=O YADSGOSSYOOKMP-UHFFFAOYSA-N 0.000 claims description 2
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 claims description 2
- 229910052753 mercury Inorganic materials 0.000 claims description 2
- 239000010959 steel Substances 0.000 claims description 2
- 229910052718 tin Inorganic materials 0.000 claims description 2
- 229910052725 zinc Inorganic materials 0.000 claims description 2
- 239000011701 zinc Substances 0.000 claims description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims 2
- 239000011133 lead Substances 0.000 claims 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims 1
- 229910052763 palladium Inorganic materials 0.000 claims 1
- 229910052709 silver Inorganic materials 0.000 claims 1
- 239000004332 silver Substances 0.000 claims 1
- 239000011135 tin Substances 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract description 18
- 238000003786 synthesis reaction Methods 0.000 abstract description 18
- 230000008569 process Effects 0.000 abstract description 10
- VQMSRUREDGBWKT-UHFFFAOYSA-N quinoline-4-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=NC2=C1 VQMSRUREDGBWKT-UHFFFAOYSA-N 0.000 abstract description 8
- TZOYXRMEFDYWDQ-UHFFFAOYSA-N 3,4-dihydro-1h-quinolin-2-one Chemical compound C1=CC=C2NC(=O)CCC2=C1 TZOYXRMEFDYWDQ-UHFFFAOYSA-N 0.000 abstract description 6
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 6
- IQQDNMHUOLMLNJ-UHFFFAOYSA-N quinolin-3-ol Chemical compound C1=CC=CC2=CC(O)=CN=C21 IQQDNMHUOLMLNJ-UHFFFAOYSA-N 0.000 abstract description 6
- LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical class C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 abstract description 4
- 239000000463 material Substances 0.000 abstract description 2
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 abstract description 2
- 238000011946 reduction process Methods 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000000203 mixture Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 238000004090 dissolution Methods 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- MHCFAGZWMAWTNR-UHFFFAOYSA-M lithium perchlorate Chemical compound [Li+].[O-]Cl(=O)(=O)=O MHCFAGZWMAWTNR-UHFFFAOYSA-M 0.000 description 4
- 229910001486 lithium perchlorate Inorganic materials 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- XNMYNYSCEJBRPZ-UHFFFAOYSA-N 2-[(3-butyl-1-isoquinolinyl)oxy]-N,N-dimethylethanamine Chemical compound C1=CC=C2C(OCCN(C)C)=NC(CCCC)=CC2=C1 XNMYNYSCEJBRPZ-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 229920000557 Nafion® Polymers 0.000 description 2
- 230000005587 bubbling Effects 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- -1 3-hydroxyquinoline compound Chemical class 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 230000000895 acaricidal effect Effects 0.000 description 1
- 239000000642 acaricide Substances 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000008236 biological pathway Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 238000006056 electrooxidation reaction Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000005656 rearomatization reaction Methods 0.000 description 1
- 238000010405 reoxidation reaction Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Electrolytic Production Of Non-Metals, Compounds, Apparatuses Therefor (AREA)
Abstract
Procedimiento de hidroxilación electroquímica a partir de ácidos monocarboxílicos de quinolina o sus carboxilatos, para producir hidroxi-quinolinas y quinolonas. La síntesis por vía electroquímica de hidroxi-quinolinas y quinolonas utiliza como reactivo los compuestos Acido 2-quinolínico (I) ó Acido 4-quinolínico (II), o sus correspondientes carboxilatos. Dicha síntesis se lleva a cabo mediante un proceso de reducción electroquímica y da lugar a los compuestos derivados de hidroxi-quinolinas y quinolonas 3,4-dihidro-2-quinolona y 3-hidroxi-quinolina (IV). En la síntesis se puede utilizar muy diversos materiales como cátodos y ánodos. El catolito y anolito pueden estar separados, o no, por una membrana selectiva, no selectiva o un diafragma. El catolito consiste en una disolución acuosa, o no, de uno de los compuestos de partida I ó II y un electrolito adecuado. El anolito consiste en una disolución acuosa, o no, de un electrolito adecuado. La electrolisis se realiza entre 0 y 90°C, a un pHentre 0 y 14, con una densidad de corriente entre 1 mA/cm2 y 2 A/cm2 y/o un potencial de cátodo entre (-0.5)V y (-3.0)V frente a Ag/AgCl.Electrochemical hydroxylation process from quinoline monocarboxylic acids or their carboxylates, to produce hydroxy-quinolines and quinolones. The electrochemical synthesis of hydroxy-quinolines and quinolones uses the compounds 2-quinolinic acid (I) or 4-quinolinic acid (II) as a reagent, or their corresponding carboxylates. Said synthesis is carried out by an electrochemical reduction process and gives rise to compounds derived from hydroxyquinoline and quinolones 3,4-dihydro-2-quinolone and 3-hydroxyquinoline (IV). In the synthesis you can use very different materials such as cathodes and anodes. The catholyte and anolyte may or may not be separated by a selective, non-selective membrane or a diaphragm. The catholyte consists of an aqueous solution or not of one of the starting compounds I or II and a suitable electrolyte. The anolyte consists of an aqueous solution or not of a suitable electrolyte. The electrolysis is performed between 0 and 90 ° C, at a pH between 0 and 14, with a current density between 1 mA / cm2 and 2 A / cm2 and / or a cathode potential between (-0.5) V and (-3.0 ) V vs. Ag / AgCl.
Description
Procedimiento de hidroxilación electroquímica a partir de ácidos monocarboxílicos de quinolina o sus carboxilatos, para producir hidroxi-quinolinas y quinolonas.Electrochemical hydroxylation procedure a from quinoline monocarboxylic acids or their carboxylates, to produce hydroxy-quinolines and quinolones.
La presente invención tiene por objeto un procedimiento de hidroxilación vía reducción electroquímica a partir de los compuestos Ácido 2-quinolínico (I) ó Ácido 4-quinolínico (II), o sus correspondientes carboxilatos, mediante el cual se obtienen los derivados de hidroxi-quinolinas y quinolonas 3,4-dihidro-2-quinolona (III) y 3-hidroxi-quinolina (IV).The present invention aims at a hydroxylation procedure via electrochemical reduction a from the compounds 2-quinolinic acid (I) or 4-quinolinic acid (II), or its corresponding carboxylates, by which derivatives of hydroxy-quinolines and quinolones 3,4-dihydro-2-quinolone (III) and 3-hydroxyquinoline (IV).
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Los procedimientos de hidroxilación electroquímica para diferentes tipos de reactivos no son muy abundantes y mayoritariamente se pueden englobar en dos tipos generales de procesos. En primer lugar, los procesos que se llevan a cabo mediante oxidación electroquímica (James H. P. Utley et al.; Acta Chem. Scand. 53 (10) 901-909 (1999)) que presentan el inconveniente del riesgo de una posterior oxidación del producto una vez ha sido hidroxilado, lo que ha provocado una intensa búsqueda de catalizadores que permitan bloquear la posterior reoxidación de los productos (A. Nasreen et al.; Heterocycl. Commun. 7, 501-506 (2001)). En segundo lugar, los procesos que copian las rutas biológicas y simulan procesos enzimáticos de hidroxilación (L. Ridder et al.; J. Am. Chem. Soc. 120 (30) 7641-7642 (1998)).The electrochemical hydroxylation procedures for different types of reagents are not very abundant and they can be mostly included in two general types of processes. First, the processes that are carried out by electrochemical oxidation (James HP Utley et al .; Acta Chem. Scand. 53 (10) 901-909 (1999)) that present the disadvantage of the risk of a subsequent oxidation of the product once it has been hydroxylated, which has caused an intense search for catalysts that allow the subsequent reoxidation of products to be blocked (A. Nasreen et al .; Heterocycl. Commun. 7, 501-506 (2001)). Second, the processes that copy the biological pathways and simulate enzymatic hydroxylation processes (L. Ridder et al .; J. Am. Chem. Soc. 120 (30) 7641-7642 (1998)).
La obtención de derivados de hidroxi-quinolinas y quinolonas se puede realizar con buen rendimiento a partir de quinoleina por hidroxilación directa con KOH a alta temperatura dando lugar a la formación de H_{2} como subproducto (J. J. M. Vanderwalle et al.; Chem. Ber. 108, 3898 (1975)). Respecto a este tipo de síntesis, el procedimiento de hidroxilación planteado en esta solicitud de patente aporta dos grandes ventajas. Por un lado, evita el uso de agentes fuertemente oxidantes y altas temperaturas, lo que supone unas condiciones de reacción extremas no siempre compatibles con otros reactivos y posteriores reacciones asociadas. Por otro lado, aporta la posibilidad de orientar selectivamente el grupo (OH) sobre el núcleo de quinoleina en función de cual sea el compuesto de partida. Por tanto, plantea una metodología de síntesis para obtener varios derivados hidroxilados. Estos derivados son importantes compuestos intermedios en síntesis farmacéutica, tanto de compuestos antiinflamatorios como inhibidores de alergias (JP 09328473) o vasodilatadores cerebrales (WO 0290351). Así como también estos productos se utilizan como intermedios en la síntesis de acaricidas e insecticidas (EP 56958).Obtaining hydroxyquinoline and quinolone derivatives can be carried out with good yield from quinolein by direct hydroxylation with KOH at high temperature resulting in the formation of H2 as a byproduct (JJM Vanderwalle et al .; Chem. Ber . 108, 3898 (1975)). With regard to this type of synthesis, the hydroxylation process outlined in this patent application provides two great advantages. On the one hand, it avoids the use of strongly oxidizing agents and high temperatures, which implies extreme reaction conditions not always compatible with other reagents and subsequent associated reactions. On the other hand, it provides the possibility of selectively targeting the group (OH) on the quinolein nucleus depending on the starting compound. Therefore, it proposes a synthesis methodology to obtain several hydroxylated derivatives. These derivatives are important intermediate compounds in pharmaceutical synthesis, both of anti-inflammatory compounds and allergy inhibitors (JP 09328473) or cerebral vasodilators (WO 0290351). As well as these products are used as intermediates in the synthesis of acaricides and insecticides (EP 56958).
El procedimiento de la presente invención
consiste en la síntesis por vía electroquímica de compuestos
derivados de hidroxi-quinolinas y quinolonas
utilizando como reactivo los compuestos I ó II, o sus
correspondiente carboxilatos. Dicha síntesis se lleva a cabo
mediante reducción electroquímica y da lugar a la obtención de los
compuestos III y
IV.The process of the present invention consists in the electrochemical synthesis of compounds derived from hydroxyquinolines and quinolones using as reagent compounds I or II, or their corresponding carboxylates. Said synthesis is carried out by electrochemical reduction and results in obtaining compounds III and
IV.
Las novedades que presenta esta invención son el empleo de la reducción electroquímica para la síntesis de derivados hidroxilados y la orientación selectiva del grupo (OH) sobre el núcleo de quinolina en función del reactivo de partida utilizado.The novelties presented by this invention are the use of electrochemical reduction for the synthesis of derivatives hydroxylates and the selective orientation of the group (OH) on the quinoline core depending on the starting reagent used.
Como principales ventajas este método de síntesis presenta: El uso de reactivos de menor peligrosidad que las rutas de síntesis usuales, condiciones de reacción poco enérgicas que no requieren altas temperaturas ni fuertes agentes oxidantes, así como la obtención del producto tras no más de dos etapas de reacción.As main advantages this method of synthesis presents: The use of reagents of less danger than the routes of usual synthesis, not very energetic reaction conditions that do not they require high temperatures or strong oxidizing agents, as well as obtaining the product after no more than two reaction stages.
La síntesis se realiza por electrorreducción de uno de los compuestos de partida I o II, o sus correspondientes carboxilatos, disuelto en una disolución acuosa, o no, junto a un electrolito adecuado (catolito). Tras la etapa electroquímica, en algunos casos, es necesario mantener la disolución catolito final almacenada en atmósfera abierta (en presencia de O_{2}) durante 48 horas para que se produzca una etapa química de rearomatización del núcleo de quinolina. Así mismo, el anolito está formado por una disolución acuosa, o no, de un electrolito adecuado.The synthesis is carried out by electroreduction of one of the starting compounds I or II, or their corresponding carboxylates, dissolved in an aqueous solution, or not, together with a suitable electrolyte (catholyte). After the electrochemical stage, in In some cases, it is necessary to maintain the final catholyte solution stored in an open atmosphere (in the presence of O2) for 48 hours for a chemical stage of rearomatization of the quinoline core. Likewise, the anolyte is formed by a aqueous solution or not of a suitable electrolyte.
El sistema de electrosíntesis está formado por uno o varios cátodos que pueden ser: grafito u otro material carbonoso, estaño, zinc, plomo, mercurio, cobre, titanio, oro, platino, titanio platinizado, hierro, acero o aleación donde intervengan los anteriores. Así mismo, lo forman uno o varios ánodos cuya naturaleza puede ser: grafito u otro material carbonoso, plomo, ánodos dimensionalmente estables, platino, titanio platinizado, PbO_{2}, SnO_{2}, DSA® o cualquier otro óxido e incluso ánodos de difusión empleando H_{2} o cualquier otro gas oxidable.The electrosynthesis system is formed by one or more cathodes that can be: graphite or other material carbonaceous, tin, zinc, lead, mercury, copper, titanium, gold, platinum, platinized titanium, iron, steel or alloy where the previous ones intervene. Likewise, it is formed by one or several anodes whose nature can be: graphite or other carbonaceous material, lead, dimensionally stable anodes, platinum, platinized titanium, PbO2, SnO2, DSA® or any other oxide and even anodes diffusion using H2 or any other oxidizable gas.
Las disoluciones de catolito y anolito pueden estar separadas, o no, por membranas selectivas a iones o cualquier otro tipo de separador.Catolite and anolyte solutions can be separated, or not, by ion selective membranes or any Other type of separator.
El número de electrodos puede ser variable. Así mismo, éstos pueden ser planos, expandidos o de cualquier forma o estructura. Pueden estar dispuestos en cualquier geometría. También pueden ser electrodos tridimensionales porosos o formar un lecho compacto o fluidizado.The number of electrodes can be variable. So same, these can be flat, expanded or in any way or structure. They can be arranged in any geometry. Too they can be porous three-dimensional electrodes or form a bed compact or fluidized.
Las conexiones eléctricas al reactor pueden corresponder a un montaje monopolar, bipolar o mixto.The electrical connections to the reactor can correspond to a monopolar, bipolar or mixed assembly.
La temperatura a la que se realiza la electrolisis estará comprendida entre los 0 y 90ºC.The temperature at which the Electrolysis will be between 0 and 90 ° C.
El pH de las disoluciones catolito y anolito puede estar comprendido entre 0 y 14.The pH of the catholyte and anolyte solutions It can be between 0 and 14.
La densidad de corriente se elegirá entre 1mA/cm^{2} y 2A/cm^{2}. Esta puede mantenerse constante o no durante la electrolisis.The current density will be chosen from 1mA / cm2 and 2A / cm2. This can be kept constant or not. during electrolysis.
El potencial del cátodo se elegirá entre (-05)V y (-3.0)V frente al electrodo de referencia AgCl/Ag. Este puede mantenerse constante o no durante la electrolisis.The cathode potential will be chosen from (-05) V and (-3.0) V against the reference electrode AgCl / Ag. This can be kept constant or not during the electrolysis.
A continuación se detallan dos ejemplos que ilustran el procedimiento de esta invención sin que esto deba ser considerado como una limitación del objeto de la invención.Below are two examples that illustrate the process of this invention without this being considered as a limitation of the object of the invention.
Utilizando como reactor electroquímico una célula de vidrio de dos compartimentos en hache con capacidad para 125ml de disolución cada compartimento, con un cátodo cilíndrico de grafito con área 7 cm^{2} y con un ánodo plano de Platino con área 1.8 cm^{2}. La membrana de separación de los dos compartimentos es una membrana selectiva a cationes (Nafion 117). La composición de la disolución inicial del catolito es 0.0132 M de Carboxilato-2-Quinolínico de litio (I) y 0.5 M de Perclorato de Litio, usando como disolvente Metanol y con un pH inicial 10.7. La composición de la disolución inicial del anolito es 0.5 M de Perclorato de Litio disuelto en Metanol y 1g de Carbonato de sodio insoluble. Durante todo el proceso de electrolisis se mantiene agitación magnética y burbujeo de N_{2} en el interior del compartimento catódico.Using a cell as an electrochemical reactor of two compartments in glass with capacity for 125ml of dissolution each compartment, with a cylindrical cathode of graphite with area 7 cm2 and with a flat Platinum anode with area 1.8 cm2. The separation membrane of the two compartments is a cation selective membrane (Nafion 117). The composition of the Initial catholyte dissolution is 0.0132 M of Lithium Carboxylate-2-Quinolinic (I) and 0.5 M of Lithium Perchlorate, using as methanol solvent and with an initial pH 10.7. The composition of the initial dissolution of the Anolyte is 0.5 M of Lithium Perchlorate dissolved in Methanol and 1g of Insoluble sodium carbonate. Throughout the process of Electrolysis is maintained magnetic stirring and bubbling of N2 inside the cathode compartment.
El potencial del cátodo se mantuvo constante durante toda la electrolisis a -1.6V vs. AgCl/Ag. El tiempo total de electrolisis fue 8h y 15 min.The cathode potential remained constant throughout the electrolysis at -1.6V vs. AgCl / Ag. Total time Electrolysis was 8h and 15 min.
Una vez finalizada la reacción se almacena la disolución catolito en atmósfera abierta durante 48 horas y posteriormente se procede a la separación del producto. Para ello se toma la disolución catolito final y se evapora todo el disolvente a presión reducida. A continuación se disuelve el precipitado obtenido con una mezcla (Diclorometano:Metanol) (5:1) y silica gel, que de nuevo se lleva a sequedad para obtener la silica impregnada con los compuestos de la síntesis. Posteriormente, se realiza la separación cromatográfica del producto en columna de silica gel. Utilizando como eluyente de la separación (Diclorometano:Metanol) (5:1) se recogen diferentes fracciones que seguidamente se analizan y se agrupan para conseguir obtener el compuesto 3,4-dihidro-2-quinolona puro. Finalmente se obtuvieron 117 mg de 3,4 dihidro-2-quinolona.Once the reaction is finished, the catholyte solution in open atmosphere for 48 hours and subsequently the product is separated. To do this take the final catholyte solution and evaporate all the solvent to reduced pressure Then the precipitate obtained is dissolved with a mixture (Dichloromethane: Methanol) (5: 1) and silica gel, which of again it is taken to dryness to obtain the silica impregnated with the Synthesis compounds Subsequently, the separation is performed Chromatographic product of silica gel column. Using as eluent of the separation (Dichloromethane: Methanol) (5: 1) is collect different fractions that are then analyzed and group to get the compound 3,4-dihydro-2-quinolone pure. Finally, 117 mg of 3.4 were obtained. dihydro-2-quinolone.
El rendimiento en materia es un 73%.The yield in matter is 73%.
EM (m/z (%)): 147 (M^{+}, 100), 118 (M^{+}-CHO, 68), 104 (M^{+}-C_{2}H_{3}O, 15).MS (m / z (%)): 147 (M +, 100), 118 (M + - CHO, 68), 104 (M + - C 2 H 3 O, 15).
RMN-H^{1} (CDCl_{3}, 300MHz), \delta (ppm): 2.64 (t, 2H), 2.96 (t, 2H), 3.11 (s, 1H), 6.87 (d, 1H), 6.98 (t, 1H), (7.14-7.19) (m, 2H).1 H NMR (CDCl 3, 300MHz), δ (ppm): 2.64 (t, 2H), 2.96 (t, 2H), 3.11 (s, 1H), 6.87 (d, 1H), 6.98 (t, 1H), (7.14-7.19) (m, 2H).
RMN-C^{13} (CDCl_{3}, 300MHz), \delta (ppm): 25.3 (CH_{2}Ar)), 30.7 (CH_{2}CO), 115.5 (ArC), 123.1 (ArC), 123.6(ArC), 127.5 (ArC), 127.9 (ArC), 137.2 (ArC), 171.9 (CO).13 C-NMR (CDCl 3, 300MHz), δ (ppm): 25.3 (CH 2 Ar)), 30.7 (CH 2 CO), 115.5 (ArC), 123.1 (ArC), 123.6 (ArC), 127.5 (ArC), 127.9 (ArC), 137.2 (ArC), 171.9 (CO).
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Utilizando como reactor electroquímico una célula de vidrio de dos compartimentos en hache con capacidad para 125m1 de disolución cada compartimento, con un cátodo cilíndrico de grafito con área 7 cm^{2} y con un ánodo plano de Platino con área 1.8 cm^{2}. La membrana de separación de los dos compartimentos es una membrana selectiva a cationes (Nafion 117). La composición de la disolución inicial del catolito es 0.0143 M de Ácido-4-quinolínico (II) y 0.5 M de Perclorato de Litio, usando como disolvente una mezcla (50:50) (Agua:Acetonitrilo) con un pH inicial 12. La composición de la disolución inicial del anolito es 0.5 M de Perclorato de Litio disuelto en Acetonitrilo y 1g de Carbonato de sodio insoluble. Durante todo el proceso de electrolisis se mantiene agitación magnética y burbujeo de N_{2} en el interior del compartimento catódico.Using a cell as an electrochemical reactor of two compartments glass in ax with capacity for 125m1 of dissolution each compartment, with a cylindrical cathode of graphite with area 7 cm2 and with a flat Platinum anode with area 1.8 cm2. The separation membrane of the two compartments is a cation selective membrane (Nafion 117). The composition of the Initial catholyte dissolution is 0.0143 M of 4-quinolinic acid (II) and 0.5 M of Lithium Perchlorate, using as a solvent a mixture (50:50) (Water: Acetonitrile) with an initial pH 12. The composition of the Initial solution of the anolyte is 0.5 M Lithium Perchlorate dissolved in Acetonitrile and 1g of insoluble sodium carbonate. Stirring is maintained throughout the electrolysis process. magnetic and bubbling of N 2 inside the compartment cathodic
El potencial del cátodo se mantuvo constante durante toda la electrolisis a -1.6V vs. AgCl/Ag. El tiempo total de electrolisis fue 7 h y 30 min.The cathode potential remained constant throughout the electrolysis at -1.6V vs. AgCl / Ag. Total time of electrolysis was 7 h and 30 min.
Una vez finalizada la reacción de síntesis la disolución catolito permanece almacenada en atmósfera abierta durante 48 horas y posteriormente se procede a la separación del producto. Para ello se toma la disolución catolito final y se evapora todo el disolvente a presión reducida. A continuación se disuelve el precipitado obtenido con una mezcla (Cloroformo: Metanol) (10:1) y silica gel, que de nuevo se lleva a sequedad para obtener la silica impregnada con los compuestos de la síntesis. Posteriormente, se realiza la separación cromatográfica del producto en columna de silica gel. Utilizando como eluyente de la separación (Cloroformo:Metanol) (10:1) se recogen diferentes fracciones que seguidamente se analizan y se agrupan para conseguir obtener el compuesto 3-hidroxi-quinolina (IV) puro. Finalmente se obtuvieron 65 mg de 3-hidroxiquinolina.Once the synthesis reaction is finished the catholyte solution remains stored in an open atmosphere for 48 hours and then proceed to separate product. For this, the final catholyte solution is taken and evaporate all solvent under reduced pressure. Then you dissolves the precipitate obtained with a mixture (Chloroform: Methanol) (10: 1) and silica gel, which is again taken to dryness to obtain the silica impregnated with the synthesis compounds. Subsequently, the chromatographic separation of the product is performed in silica gel column. Using as eluent of separation (Chloroform: Methanol) (10: 1) different fractions are collected that then they are analyzed and grouped to get the 3-hydroxyquinoline compound (IV) pure. Finally 65 mg of 3-hydroxyquinoline.
El rendimiento en materia es un 52%.The yield in matter is 52%.
EM (m/z (%)): 145 (M^{+}, 100), 117 (M^{+}-CO, 14), 90 (M^{+}-C_{2}HON, 28).MS (m / z (%)): 145 (M +, 100), 117 (M + - CO, 14), 90 (M + - C 2 HON, 28).
RMN-H^{1} (CD_{3}OD, 300MHz), \delta (ppm): 7.15 (d, 1H), 7.19-7.34 (m, 2H), 7.51 (d, 1H), 7.73 (d, 1H), 8.36 (d, 1H).1 H NMR (CD 3 OD, 300MHz), δ (ppm): 7.15 (d, 1H), 7.19-7.34 (m, 2H), 7.51 (d, 1H), 7.73 (d, 1H), 8.36 (d, 1H).
RMN-C^{13} (CD_{3}OD, 300MHz), \delta (ppm): 117.9 (CHAr), 127.6 (ArC), 127.7 (ArC), 128.2 (ArC), 128.8 (ArC), 131.0 (ArC), 143.6 (ArC), 144.4 (CHN), 152.6 (COH).13 C-NMR (CD 3 OD, 300MHz), δ (ppm): 117.9 (CHAr), 127.6 (ArC), 127.7 (ArC), 128.2 (ArC), 128.8 (ArC), 131.0 (ArC), 143.6 (ArC), 144.4 (CHN), 152.6 (COH).
Claims (1)
- a)to)
- La naturaleza del cátodo puede ser: grafito u otro material carbonoso, plata, estaño, zinc, plomo, mercurio, cobre, paladio, titanio, oro, platino, titanio platinizado, hierro, acero o aleación donde intervengan los anteriores. Así mismo, pueden utilizarse como ánodos: grafito u otro material carbonoso, plomo, ánodos dimensionalmente estables, platino, titanio platinizado, PbO_{2}, SnO_{2}, DSA® o cualquier otro óxido e incluso ánodos de difusión empleando H_{2} o cualquier otro gas oxidable.The Nature of the cathode can be: graphite or other carbonaceous material, silver, tin, zinc, lead, mercury, copper, palladium, titanium, gold, platinum, platinized titanium, iron, steel or alloy where the previous ones intervene. They can also be used as anodes: graphite or other carbonaceous material, lead, anodes dimensionally stable, platinum, platinized titanium, PbO2, SnO2, DSA® or any other oxide and even diffusion anodes using H2 or any other oxidizable gas.
- b)b)
- Los electrodos pueden ser planos, expandidos o de cualquier forma o estructura. Pueden estar dispuestos en cualquier geometría. También pueden ser electrodos tridimensionales porosos o formar un lecho compacto o fluidizado.The electrodes can be flat, expanded or in any way or structure. They can be arranged in any geometry. Too they can be porous three-dimensional electrodes or form a bed compact or fluidized.
- c)C)
- El número de electrodos puede ser variable. Las conexiones eléctricas al reactor pueden corresponder a un montaje monopolar, bipolar o mixto.He number of electrodes can be variable. Electrical connections to the reactor may correspond to a monopolar, bipolar or mixed.
- d)d)
- Las disoluciones de catolito y ánolito pueden estar separadas o no por membranas selectivas a iones o cualquier otro tipo de separador.The catholyte and anolyte solutions may or may not be separated by ion selective membranes or any other type of separator.
- e)and)
- El catolito está formado por una disolución acuosa o no de uno de los compuestos de partida I ó II, o sus correspondientes carboxilatos y un electrolito adecuado. El anolito está formado por una disolución acuosa o no de un electrolito adecuado.He catholyte is formed by an aqueous solution or not of one of the starting compounds I or II, or their corresponding carboxylates and A suitable electrolyte. The anolyte is formed by a solution aqueous or not of a suitable electrolyte.
- f)F)
- La temperatura a la que se realiza la electrólisis estará comprendida entre los 0 y 90ºC.The temperature at which the electrolysis is performed will be included between 0 and 90 ° C.
- g)g)
- La densidad de corriente se elegirá entre 1mA/cm^{2} y 2A/cm^{2}. Esta puede mantenerse constante o no durante la electrolisis.The Current density will be chosen between 1mA / cm2 and 2A / cm2. This can be kept constant or not during the electrolysis.
- h)h)
- El pH de las disoluciones catolito y anolito puede estar comprendido entre 0 y 14.PH of the catholyte and anolyte solutions can be comprised between 0 and 14
- i)i)
- El potencial del cátodo se elegirá entre (-0.5)V y (-3.0)V frente al electrodo de referencia AgCl/Ag. Este puede mantenerse constante o no durante la electrolisis.He cathode potential will be chosen between (-0.5) V and (-3.0) V against the reference electrode AgCl / Ag. This can stay constant or not during electrolysis.
- j)j)
- Los productos de la hidroxilación electroquímica, en algunos casos, pueden obtenerse tras una etapa de almacenamiento de la disolución catolito en atmósfera abierta durante al menos 48 horas.The products of electrochemical hydroxylation, in some cases, can be obtained after a storage stage of the solution catholyte in an open atmosphere for at least 48 hours.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3453332A (en) * | 1967-11-29 | 1969-07-01 | Universal Oil Prod Co | Hydroxylation of aromatic compounds |
| US4096044A (en) * | 1975-03-31 | 1978-06-20 | Hooker Chemicals & Plastics Corp. | Electrochemical hydroxylation of certain aromatic compounds |
| US4718994A (en) * | 1985-06-14 | 1988-01-12 | Latviisky Gosudarstvenny Universaitet Imeni P. Stuchki | Method for preparing hydroxy compounds of aromatic and heteroaromatic series |
| US5002641A (en) * | 1990-06-28 | 1991-03-26 | Reilly Industries, Inc. | Electrochemical synthesis of niacin and other N-heterocyclic compounds |
-
2004
- 2004-02-10 ES ES200400306A patent/ES2245584B2/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3453332A (en) * | 1967-11-29 | 1969-07-01 | Universal Oil Prod Co | Hydroxylation of aromatic compounds |
| US4096044A (en) * | 1975-03-31 | 1978-06-20 | Hooker Chemicals & Plastics Corp. | Electrochemical hydroxylation of certain aromatic compounds |
| US4718994A (en) * | 1985-06-14 | 1988-01-12 | Latviisky Gosudarstvenny Universaitet Imeni P. Stuchki | Method for preparing hydroxy compounds of aromatic and heteroaromatic series |
| US5002641A (en) * | 1990-06-28 | 1991-03-26 | Reilly Industries, Inc. | Electrochemical synthesis of niacin and other N-heterocyclic compounds |
Non-Patent Citations (1)
| Title |
|---|
| A. NASREEN et al. "An efficient facile and selective hydroxylation of nitrogen heterocycles", Heterocyclic Communications, 2001, Vol. 7, Nº 5, páginas 501-506. * |
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