y iii) heterogeneizacion o inmovilizacion de complejo metalico soluble a soportes insolubles, tanto organicos como inorganicos. En general, estos intentos no han resultado en procesos comercialmente viables por diversos motivos, encontrando que los mas frecuentes son el lixiviado del centro activo y/o su degradaciOn, que resultan en la 5 contaminaciOn metalica de los productos y/o en perdidas fatales de productividad, actividad y selectividad. El caso particular de paladio, conocido por su utilidad para catalizar un rango annplio de transformaciones en sintesis organica, convencionalmente asociado a ligandos 10 organofosforados, no es una excepciOn: son muy pocos los procesos industriales implantados en los que intervienen sus complejos solubles (de Vries, J. G. 2012) y en ellos generalmente ha sido necesario desarrollar procedimientos especificos y costosos para eliminar los restos t6xicos metalicos y fosforados. Segan de Vries, en el lustro anterior a 2012 solo el 6-7% de las etapas sinteticas de la industria farmaceutica 15 implicaron la catalisis homogenea, destacando que el 50% de ellas correspondian a los farmacos introducidos mas recientemente. Seria por lo tanto deseable disponer de catalizadores, en particular de paladio y libres de ligandos fosforados, que combinen un comportamiento distintivo con altos valores de 20 TON (del ingles turnover number), con los que Ilegar a implementar "producciones limpias" en las que se puedan separar facil y eficientemente posibilitando su reutilizaciOn, o su uso en continuo, y en las que se pueda prescindir de las costosas operaciones de purificaciOn metalica de los productos. 25 Unos ligandos que recientemente han aparecido como una alternativa muy atractiva a los organofosforados son los de tipo carbeno N-heterociclico (NHC). Los NHCs proporcionan enlaces fuertes, que resultan en complejos metalicos muy robustos y excelentes para catalizar un rango muy amplio de procesos en fase homogenea, en los que las caracteristicas estereo-electronicas del ligando juegan un papel estabilizador importante 30 (Diez-Gonzalez, S., etal. 2009). Para inmovilizar catalizadores metalicos, entre otros soportes disponibles en la actualidad, se han utilizado nanoparticulas magneticas (NPMs) con diversos tipos de ligandos anclados covalentemente a la superficie, (Baig, R. B. N., et al. 2013; Shylesh, S., et al. 35 2010). Existen tambien descripciones en las que se han empleado complejos NHC de paladio heterogeneizados a traves de grupos alquilsilOxido sobre NPMs desnudas 3
(Stevens, P. D., et al. Chem. Commun. 2005; Zheng, Y., et al. 2006), mediante grupos bencilo sobre NPMs recubiertas de poliestireno (Stevens, P. D., et al. Org. Lett. 2005), y grupos arilsiloxano sobre microesferas magneticas (Yang, H., et al. 2012) o NPMs recubiertas de silice (Yang, H., et al. 2011). Se ha demostrado que todos ellos son 5 activos en diversas reacciones de acoplamiento cruzado (i.e., Suzuki-Miyaura, Heck-Mizoroki y Sonogashira), son recuperables magneticamente y la mayoria han sido reutilizados. De los anteriores solo en un caso (Yang, H., etal. 2011) se ha determinado el contenido de paladio en los productos, pero Onicamente tras el primer uso del catalizador. En todos ellos el procedimiento de soportado del complejo metalico sigue la 10 secuencia: 1) funcionalizaciOn del soporte con sales de imidazolio, que son precursoras de ligandos NHC; 2) metalaciOn del soporte funcionalizado anterior con acetilacetonato o acetato de paladio aPd(acac)2] 6 [Pd(OAc)2]). La desventaja de esta metodologia, que por otro lado es la habitual con cualquier tipo de soporte y ligando, es la imposibilidad de poder controlar tanto la formacion de corrplejos con un Onico entorno de coordinaciOn, 15 como la presencia de restos metalicos adsorbidos y no anclados covalentemente. En este sentido, recientennente se ha comprobado que, usando gel de silice como soporte, los resultados cataliticos son mucho mejores cuando se inmoviliza el complejo NHC de paladio preformado que cuando este se sintetiza sobre la superficie del gel de silice (Tyrrell, E., etal. 2011). 20 La presente invenciOn propone la preparacion de nuevos complejos NHC de paladio (CPs) y su heterogeneizaciOn a posteriori sobre particulas magneticas (PMs) de 6xido de hierro, junto a su utilizacion en reacciones de acoplamiento cruzado. El metodo proporciona especies metalicas (micas bier, definidas, en las que los ligandos NHC fijan 25 fuertemente los centros metelicos y los protegen durante la catalisis, a la vez que se encuentran soportadas covalentemente a traves de grupos inertes "Y" a particulas recubiertas de un material tambien inerte, mientras que el superparamagnetismo del nude° de la particula a la que estan asociadas permite su separacion del medio aplicando un campo magnetic°. Estas particulas magneticas con los catalizadores 30 soportados (PMCs) dan lugar a dispersiones estables en agua, catalizan reacciones de acoplamiento carbono-carbono en medio acuoso en condiciones suaves, incluso con cloruros de arilo, se recuperan sin degradaciOn por simple separaci6n magnetica, se pueden reutilizar Ilegando a valores de TON muy elevados y no sufren lixiviado metalico. 35 Referente a precursores de ligandos NHC sustituidos por grupos complementarios (Gc) terminales y semejantes o necesarios pare sintetizar CPs de los tipos I-111, se ha descrito 4
una sal de imidazolio sustituida con una amina protegida en forma de grupo ftalimido (Harjani, J. R., et al. 2008), otras tres sustituidas con una amina primaria como grupo complementario "G" (Busetto, L. et al. 2008; Ballarin, B., et al. 2012; Ohara, H., et al. 2012), otras cinco en las que ese grupo es trietoxisililo (Chi, Y. S., et al. 2004; Trilla, M., et 5 al. 2009; Borja, G., et al. 2012, Berardi, S., et al. 2010) y otras cinco en la que es trimetoxisililo (Kunze, K., et al. PCT/US2011/046155, Tyrrell, E., et al. 2011). Como precursores necesarios para la sintesis de complejos de tipo III, se han descrito la sintesis de bis(azolil)alcanos (Diez-Barra, E , etal. Heterocycles 1992, 34, 1365-1373). 10 Se conoce un Unico ejemplo de CP mono(NHC) relacionado con la formulaciOn del tipo I, concretamente con el ligando NHC sustituido por una cadena con un "G' = trietoxisililo (Borja, G., etal. 2012), aunque se han descrito otros complejos relacionados pero sin ese tipo de sustitucion (Organ, M. G., et al. CA2556850A1). 15 Se han descrito CPs bis(NHC) con la estructura referida como de tipo II en los que el "G" es trialcoxisililo, utilizando procedimientos semejantes (Kunze, K., et a/. PCT/US2011/046155; Tyrrell, E., etal. 2011; Berardi, S., etal. 2010), o distintos (Yang, H., et al. 2009; Polshettiwar, V., et al. 2008; Corma, A., et al. 2007; Lee, S.-M., et al. 2007, 79; Karimi, B., et al. 2006), a los empleados en el contexto de la presente invenciOn. En 20 los serialados como procedimientos semejantes, la sintesis se realiza a traves de complejos intermedios de plata, que se preparan siguiendo el metodo estandar descrito por Lin (Wang, H. M. J., et al. 1998), pero en ningOn caso se asilan, purifican y caracterizan estos agentes de transferencia de carbeno, a diferencia del procedimiento propuesto en la presente invenciOn. No se ha descrito ningim CP de tipo III con 25 alcoxisililos como "G", ni se conocen de los tipos aqui referidos como II y III en los que ese grupo es una amina primaria, a pesar de que ambas topologias de complejos de paladio, quelato o no, son abundantes en la bibliografia. Se han descrito procedimientos para soportar CPs preformados de los tipos I y II ya 30 referenciados (i.e., Gc = Si(OR)3) sobre silicas de distinta naturaleza, o para incorporarlos en materiales compuestos mediante condensaciones sol-gel, pero en ningun caso para generar PMCs. Como se ha mencionado, si se han preparado PMCs funcionalizadas con precursores de NHCs inmovilizados a ?saves de grupos alcoxisililo sobre distintos soportes que posteriormente han sido metalados con una fuente de paladio, pero ninguno 35 sobre particulas magneticas recubiertas de silice de ningun tipo, existiendo un ejemplo de fijaciOn a este tipo de materiales a traves de enlaces arilsiloxano como precedente mas 5
cercano (Yang, H., 2011). En todos ellos el procedimiento de inmovilizaciOn utilizado impide conocer la identidad y uniformidad estructural de los complejos soportados. Finalmente, tambien se ha descrito un procedimiento para soportar complejos dendriticos 5 de tipo fosfano de paladio, con una amina primaria en el punto focal del dendrOn, sobre PMs recubiertas de polimero con grupos acid° carboxilico como "Gs" (Rosario-Amorin, D., et al. 2012). Las PMCs basadas en ligandos NHC mencionadas, aunque con una estructura del 10 entomb del paladio indeterminada, han demostrado ser activos en diversos procesos de acoplamiento cruzado en diversas condiciones de reaccion, son recuperables magneticamente y la mayoria han sido reutilizados. SOlo en un caso (Yang, H., 2011) se ha determinado el lixiviado de paladio a los productos y unicamente tras el primer uso del catalizador. 15 DESCRIPCION DE LA INVENCION La presente invenciOn comprende un procedimiento de preparaciOn de nuevos CPs que, una vez formados, se pueden heterogeneizar sobre PMs, proporcionando PMCs con 20 especies de paladio Cmicas, bien definidas y fijadas fuertemente al soporte. Las PMCs se caracterizan por dar lugar a dispersiones estables en agua, son activas en procesos cataliticos de formaci6n de enlaces carbono-carbono en medio acuoso y en condiciones suaves, el superparamagnetismo del nixie° de las particulas permite su separacion de los productos aplicando un campo magnetico, se recuperan sin degradaci6n, se pueden 25 reutilizar Ilegando a valores de TON muy elevados y no sufren lixiviado metalico, o es insignificante, resultando en productos de la catalisis con contenidos de paladio por debajo de 10 ppm en masa (hasta niveles de unos ppb) tras la separaci6n magnetica de las particulas. 30 En un primer aspecto la invenciOn esta relacionada con nuevos CPs que presentan las tipologias I, II y III. 35 En un segundo aspecto la invenciOn esta, relacionada con los metodos de sintesis de dichos CPs de los tipos I, II y III y de sus precursores. En un tercer aspecto la invencion esta relacionada con los procedimientos de 6
inmovilizacion de esos CPs de los tipos I, II y III sobre particulas magneticas (PMs) de 6xido de hierro para generar particulas magneticas con los complejos soportados (PMCs). En un cuarto aspecto la invenciOn tambien esta relacionada con el uso de dichas PMCs 5 como catalizadores de reacciones de acoplamiento carbono-carbono, y sus caracteristicas en relaciOn con su separaciOn de los productos, su reutilizaciOn, su productividad y su alta resistencia a la degradaciOn y al lixiviado. 10 PM CP PMC DESCRIPCIoN DETALLADA DE LA INVENCION Especificamente, la invencion comprende la sintesis de CPs con ligandos NHC 15 sustituidos por grupos complementarios (Gc) terminales de una cadena alquilica y Utiles para la formaciOn de una uniOn covalente "Y" al soporte, la inmovilizaciOn post-sintetica de los complejos a PMs que poseen un recubrimiento que contiene grupos superficiales (Gs) adecuados para formar el anclaje "Y", y el uso de estas PMCs en ciclos de catalisis-recuperaciOn-reutilizaciOn en reacciones de activaciOn de haluros de arilo. 20 Concretamente, el CP a soportar comprende complejos mono(NHC), bis(NHC) y bis(NHC)-quelato, en los que "L" es un ligando monodentado neutro L' con nitr6geno dador (tipo I), preferentemente una piridina, y "R" es un sustituyente alquilo o arilo o alquilarilo, o "L" es otro ligando anclante NHC con el mismo "R" (tipo II), o "L" es otro 25 ligando anclante NHC en el que "R" es una cadena alquilica puente entre los dos ligandos NHC (tipo III), respectivamente. En ellos "X" es un sustituyente monoaniOnico, preferentemente un haluro, y "Gc" es un grupo funcional susceptible de sufrir reacciones de condensacion, preferentemente un trialcoxisililo o amina primaria, que se encuentra al final de una cadena alquilica de n carbonos, preferentemente entre 1 y 4. Particularmente, 30 en los CPs quelato (tipo III) los anillos heterociclicos se encuentra unidos a traves de una cadena alquilica de n' eslabones, preferentemente entre 1 y 3. 7
Gc N N y 'FR X-Pd-X L' Gc,opy N X-Pd-X R NN GC Pd A‘ Gc"( x' \ X Th-Gc Las PMs utilizadas corn° soporte son comercialmente disponibles y se caracterizan por 5 diametros en el rango de decenas a centenas de nanOmetros, preferentemente 100-500 nm, por un nixie° de un 6xido de hierro, preferentemente maghemita, y por un recubrimiento inerte como silice o poliestireno funcionalizados con "Gs", preferentemente silanoles y acidos carboxilico, respectivamente. 10 Adicionalmente, el procedimiento de inmovilizaciOn consiste en reacciones de condensaciOn, preferentemente con formaciOn de grupos siloxano o amida, entre los CPs y las correspondientes PMs dispersadas en disolventes organicos, o preferentemente en un medio acuoso en presencia de pequerias cantidades de surfactantes no i6nicos. 15 ftal,N-T. N kin INH2NH 2 ( CH3)2CHOH N 2 PdX2/K2CO31L' CH2Cl2 Ag20 /=\ N LN/ I-ZzN fta1.14,X , A X - X- tv\ THF CH3CN ftall-/n tr ftal (R'0)3Sii+X CH2Cl2 (R'0)3S1 N. R X-Pd-X L' I(Si) P=1 N -n y AgX 3 [PdX2(L"2)] \in X-Pd-X CH2Cl2 R -1\1"tNN4Gc 8 II 4 1 Pd(OAc)2 DMS0 NLN Pd tIal-An X/ \X kftal 5 NH 2 NH2I CH3CN N-k H2N45Pd n X/ \X (N1-12 III(A)
La presente invencion tambien concierne los usos de las PMCs de la invencion en reacciones de acoplamiento carbono-carbono, particularmente de Heck-Mizoroki y Suzuki-Miyaura con haluros de arilo, dispersadas en un medio acuso y en condiciones 5 suaves, y su reutilizaciOn en catalisis tras su separacion efectiva de los productos mediante un iman externo. La sintesis de algunos de los CPs de esta invenciOn que tienen fOrmulas de los tipos I, ll y Ill puede lograrse mediante las transformaciones indicadas en el esquema anterior. Los 10 complejos especialmente preferidos ester) descritos en los ejemplos de esta invenciOn y los metodos para preparar los complejos de los tipos I-Ill y sus intermedios consiste en: a) transformar imizadoles N-sustituidos preferentemente, pero no excluyentemente, no-sustituidos en el carbono heterociclico en posici6n 2, mediante reacciones de N-15 alquilaciOn con N-(haloalquil)ftalimides, para formar y aislar sales de imidazolio 1 con aminas primarias protegidas en forma de grupo ftalimido (ftal), 1 20 donde R puede ser un grupo alquilico, arilico o alquilarilico, conteniendo entre 1 y 20 atomos de carbono, y puede estar sustituido por grupos sin protones activos (halogeno, sulfonato, carboxilato, eter, floater, cetona, sulfOxido, ester, amida, nitrilo); donde alternativamente R puede ser otra cadena con el grupo ftalimido; donde X-puede ser una especie aniOnica, preferentemente un halogenuro; y donde el 25 espaciador entre el grupo protector y el heterociclo queda definido por una longitud de cadena de n eslabones que puede ester comprendida entre 1 y 4 carbonos. b) transformer innizadoles N-sustituidos preferentemente, pero no excluyentemente, no-sustituidos en el carbono heterociclico en posiciOn 2, mediante reacciones de N-30 alquilaciOn con (haloalquil)trialcoxisilanos, para formar y aislar sales de imidazolio 2(Si) con un grupo trialcoxisililo, 9
(I:110)3Si N, R X-2(Si) donde R, X y n se han definido anteriormente en la transformaciOn a); donde alternativamente R puede ser otra cadena con el grupo trialcoxisililo; y donde R' 5 puede ser metilo o etilo. c) transformar las sales de imidazolio 1, por procedimientos convencionales de la sintesis de Gabriel (hidrOlisis acida o basica), o preferentemente por el metodo de Ing-Manske utilizando hidracina, para former y aislar sales de imidazolio 2(A) con un 10 grupo amina primaria terminal de cadena, F-----\ H2NNN.R 2(A) donde R, X y n se han definido anteriormente en la transformaciOn a); y donde 15 alternativamente R puede ser otra cadena con una amina primaria terminal. d) transformar las sales de imidazolio 2(Si), por un procedimiento patentado (Organ, M. G., etal., CA2556850A1), para formar y aislar complejos mono(NHC) de tipo 1(81), en los que el ligando carbeno se encuentra coordinado, preferente pero no 20 excluyentemente, por su carbono 2, 1=1. (Fro)3sii...),NyN,R X -Pd- X L' l(Si) donde R, X y n se han definido anteriormente en la transformed& a) y R' en la 25 transformed& b); donde alter nativamente los ligandos X pueden independientemente ser un haluro, carboxilato, hidruro, o un alquilo, alilo, arilo, alquilarilo, alcoxido, ariloxido, beta-dicetonato, tiolato sustituidos o no sustituidos; y donde L' es un ligando monodentado neutro con nitr6geno dador, preferentemente 10
una piridina que puede estar sustituida por alquilos o haluros en cualquiera de sus carbonos. e) transformar las sales de imidazolio 2(Si o A), mediante el procedimiento estandar 5 descrito por Lin (Wang, H. M. J., et al. 1998) con Oxido de plata, para formar y aislar complejos NHC de plata 3 (Si o A), en los que el ligando carbeno se encuentra coordinado, preferente pero no excluyentemente, por su carbono 2, 10 (R10)3Si,/ Ny N. R AgX 3(Si) H2N.0,nNyN R AgX 3(A) donde R, X y n se han definido anteriormente en la transformaciOn a) y R' en la transformaciOn b). f) transformar los complejos de plata 3(Si o A), mediante reacciones de 15 transmetalaciOn a precursores de paladio(ii) con ligandos Miles y de fOrmula general [PdX2L"2] (L"2 = etilendiamina, N,N,N'N'-tetrametiletilendiamina, 1,5-ciclooctadieno; o L" = benzonitrilo, acetonitrilo), para formar y aislar complejos bis(NHC) de tipo II(Si o A), en los que los ligandos carbeno se encuentran coordinados, preferente pero no excluyentemente, por su carbono 2, 20 /=\ (R0)3SiNyN,R X -Pd-X R 'N N /fiSi(OR')3 II(Si) /=\ H2NNyN,R X -Pd- X R_Pk 'N N in NH2 11(A) donde R, X y n se han definido anteriormente en la transformed& a) y R' en la transformaci6n b); y donde alternativamente los ligandos X pueden 25 independientemente ser un haluro, carboxilato, hidruro, o un alquilo, alilo, arilo, alquilarilo, alcOxido, arilOxido, beta-dicetonato, tiolato sustituidos o no sustituidos. g) transformar bis(imidazolil)alcanos, preferente pero no excluyentemente, no-sustituidos en el carbono heterociclico en posicion 2, para formar y aislar sales de 11
5 imidazolio 4 con aminas primarias protegidas en forma de grupo ftalimido (ftal) mediante reacciones de N-alquilacion con N-(haloalquil)ftalimidas, n' f NrOn (%N 0 0 4 donde X- y n se han definido anteriormente en la transformaciOn a) y el puente entre anillos imidazolicos queda definido por una longitud de cadena de n' eslabones que puede estar comprendida entre 1 y 3. 10 h) transformar las sales 4, mediante reacciones de metalaciOn en presencia de acetato de paladio, para formar y aislar complejos bis(NHC) quelato 5 con una amina primaria protegida en forma de grupo ftalimido (ftal), en los que los ligandos carbeno se encuentran coordinados, preferente pero no excluyentemente, por su carbono 2, e I\1—Pd)N NAn Xj 15 5 donde X- y n se han definido anteriormente en la transformacion a) y n' en la transformaci6n g); y donde adicionalmente los ligandos X pueden independientemente ser un haluro, carboxilato, hidruro, o un alquilo, alilo, arilo, 20 alquilarilo, alcOxido, ariloxido, beta-dicetonato, tiolato sustituidos o no sustituidos i) transformar los complejos quelato 5, por procedimientos convencionales de la sintesis de Gabriel (hidrolisis acida o basica), o preferentemente por el metodo de lng-Manske utilizando hidracina, para formar y aislar complejos bis(NHC) quelato de 25 tipo III(A) con grupos amina prinnaria terminal de cadena, en los que los ligandos carbeno se encuentran coordinados, preferente pero no excluyentemente, por su carbono 2, 12
Pd H2N4j/n X/ \ X kNH2 III(A) donde X y n se han definido anteriormente en la transformaci6n a) y n' en la 5 transformaci6n g); y donde alternativamente los ligandos X pueden independientemente ser un haluro, carboxilato, hidruro, o un alquilo, alilo, arilo, alquilarilo, alcOxido, arilOxido, beta-dicetonato, tiolato sustituidos o no sustituidos. En lo que concierne a la sintesis de PMCs de esta invencion puede lograrse nnediante 10 reacciones de condensacion entre los Gs de las PMs y los Gc correspondientes de los CPs de los tipos I, II o III. Las PMs utilizadas como soporte son comercialmente disponibles con un nude°, preferente aunque no linnitante, de maghemita (y-Fe203) y estan recubiertas de silice o, alternativamente, de poliestireno funcionalizado con grupos acid° carboxilico. Las PMCs especialmente preferidas estan descritas en los ejemplos de 15 esta invenciOn y los metodos para prepararlas consiste en: j) heterogeneizar los CPs de los tipos I(Si) y II(Si) sobre PMs recubiertas de silice, mediante la condensaciOn de los grupos trialcoxisililo de los correspondientes CPs y los grupos silanol superficiales de las PMs, para formar anclajes siloxano y aislar las 20 correspondientes PMC(Si)I y PMC(Si)II, [Pd] [Pd] [Pd] [Pd] [Pd] [Pd] FeO. [Pd] [Pd] [Pd] [Pd] [Pd] [Pd] PMC(Si)1 0, O-Si N N'R 0' 1`);) y X—Pd-X L' l(Si)-anclado 13
[Pd] [Pd] [Pd] [Pd] [Pd] [Pd] PMC(Si)II /=\ 0-Sid x_Ny N —0 0(1) ' X—Pd-X FOC)- II(Si)-anclado donde R, X y n se han definido anteriormente en la transformaciOn a) y L" en la transformaciOn d); y donde alternativamente los ligandos X pueden 5 independientemente ser un haluro, carboxilato, hidruro, o un alquilo, alilo, arilo, alquilarilo, alcOxido, arilOxido, beta-dicetonato, tiolato sustituidos o no sustituidos. El procedimiento de inmovilizacion comprende la dispersi6n de las PMs en disolventes organicos, o preferentemente en un medio hidroalcohOlico en presencia 10 de pequefias cantidades de surfactantes no ionicos con balance hidrofilico-hidrofObico alto (HLB > 15, usados por debajo de su concentraciOn micelar critica), una adici6n lenta de una disoluciOn alcohOlica del CP a inmovilizar, una agitaci6n mecanica constante y una secuencia de lavados que consiste en atrapar las PMCs con un iman externo y separarlas por decantado de las disoluciones. Las PMC(S1)1 y 15 PMC(S1)11 se caracterizan por contenidos de paladio que se corresponden con en torno a 1-4 moleculas de CP inmovilizadas por nm2 de superficie. La Table 1 recoge contenidos de metal de los ejemplos de PMCs especialmente preferidos. Table 1 .Contenido de paladio en las PMC(Si)I y PMC(Si)II de los ejemplos.a PMC(Si)In° PMC(S1)11n° n°: 1 mg Pd / g MNPs 1,27 % en peso de Pd 0,28 mmol Pd / g MNPs 0,026 (Moleculas/nm2)° 1,6 2 3 1 2 3 3,59 3,07 2,39 5,07 4,25 0,77 0,66 0,24 0,51 0,43 0,072 0,062 0,022 0,048 0,040 4,3 3,7 1,3 2,9 2,4 a Determinado por ICP-MS. Desviaciones Estandar Relativas en las cuantificaciones s10%. Para PMs de 300 nm, densidad de 2 g/cm3 y una superficie especifica de 10 m2/g. k) heterogeneizar los CPs de los tipos II(A) y III(A) sobre PMs recubiertas de 14
5 poliestireno entrecruzado funcionalizadas con grupos acidos carboxilico (densidad de grupos COOH ?. 300 pmol/g), mediante la condensaciOn de los grupos amina primaria de los correspondientes CPs y los grupos acidos superficiales de las PMs, para formar anclajes amida y aislar las correspondientes PMC(A)II y PMC(A)III, [Pd] [Pd] [Pd] [Pd] [Pd] H /=\N N 0 X -Pd- X 0 N N.R N "n H [Pd] [Pd] [Pd] [Pd] [Pd] [Pd] PMC(A)II [Pd] [Pd] [Pd] PMC(A)111 [P '• [Pd] 11(A)-anclado NH OFIN X‘ Pd (>) X/ )---N nriN NH 111(A)-anclado „,,,, 10 donde R, X y n se han definido anteriormente en la transformaci6n a) y n" en la transfornnacion g); y donde alternativamente los ligandos X pueden independientemente ser un haluro, carboxilato, hidruro, o un alquilo, alilo, arilo, alquilarilo, alcoxido, ariloxido, beta-dicetonato, tiolato sustituidos o no sustituidos. 15 El procedimiento de inmovilizaciOn esta basado en una modificaci6n de un metodo descrito (Rosario-Amorin, D., et al. 2012) y comprende la dispersi6n de las PMs en un medio hidroalcohOlico en presencia de pequenas cantidades de surfactantes no ionicos con balance hidrofilico-hidrofObico alto (HLB > 15, usados por debajo de su concentracion micelar critica) en presencia de una carbodiimida como agente de 20 acoplamiento, la adici6n de una disolucion en un disolvente muy polar del CP a 15
inmovilizar, una agitacion mecanica constante y una secuencia de lavados que consiste en atrapar las PMCs con un iman externo y separarlas por decantado de las disoluciones. Las PMC(A)II ó PMC(A)III se caracterizan por contenidos de paladio que se corresponden con en tomb a 1-3 moleculas de CP inmovilizadas por nm2 de 5 superficie. La Tabla 2 recoge contenidos de metal de los ejemplos de PMCs especialmente preferidos. Tabla 2. Contenido de paladio en las PMC(A)II y PMC(A)III de los ejemplos.a mg Pd / g MNPs °A en peso de Pd mmol Pd /9 MNPs (Moleculas/nm2)° PMC(A)IIn° PMC(A)IIIn° n°: 1 2 3 4 2,58 5,38 3,60 8,12 0,26 0,54 0,36 0,81 0,024 0,046 0,031 0,076 1,0 1,8 1,6 3,1 a Determinado por ICP-MS. Desviaciones Estandar Relativas en as cuantificaciones s10%. Para PMs de 200 nm, densidad de 2 g/cm3 y una superficie especifica de 15 m2/g. Las caracteristicas esenciales de las PMCs de la presente invenciOn son que catalizan 10 reacciones de acoplamiento carbono-carbono en condiciones suaves, que se separan facilmente del medio de reacciOn, que se pueden reutilizar en series de numerosos reciclados, que son muy robustas a la degradaciOn y que apenas sufren lixiviado de paladio. Se ha realizado una exhaustiva evaluaciOn de las capacidades cataliticas de las PMCs de la presente invenciOn enfocada, pero no limitada, a reacciones modelo de 15 Heck-Mizoroki y Suzuki-Miyaura con haluros de arilo, con las que se han analizado sus perfiles cineticos (% conversion vs. tiempo), su reciclabilidad en ensayos sucesivos de catalisis-recuperaciOn-reutilizaciOn, el mantenimiento de sus propiedades en las series de reciclados y el lixiviado sufrido por las PMCs en los misnnos. Seguidamente se muestra una selecciOn de resultados, los procedimientos utilizados se describen en los ejemplos 20 de esta invenciOn y la evaluaciOn de las propiedades cataliticas consiste en: I) ensayar las PMCs de esta invenciOn en reacciones de Suzuki-Miyaura entre un acid° arilborOnico, preferentemente el fenilboronico, con haluros de arilo, preferentemente el 4-bromo- y 4-clorotolueno, a temperatura suave (65-80 °C), en un medio organico-25 acuoso agitado mecanicamente a veiocidad constante en presencia de pequenas cantidades de surfactantes no i6nicos con balance hidrofilico-hidrofobico alto (HLB > 15, usados por debajo de su concentraciOn nnicelar critica) y con cargas bajas de 16
paladio (0,024-0,050 mol% [Pd], con respect° del haloareno correspondiente usado como el sustrato limitante). La Table 3 recoge los resultados obtenidos con las PMCs especialmente preferidas. Table 3.Resultados en la reacci6n de Suzuki-Miyaura con las PMCs de los ejemplos. entrada precursor sustratoa medioD T(°C) t(h) conversion (%)a ld PMC(Si)I1 PMC(Si)I2 PMC(Si)I2 PMC(S1)13 PMC(Si)12 PMC(Si)I3 4-bromotolueno 4-bromotolueno 4-bromotolueno 4-bromotolueno 4-clorotolueno 4-clorotolueno Tx/Et0H Tx/Et0H Tx/THF Tx/Et0H Tx/Et0H Tx/Et0H 65 65 65 65 80 80 2 2 2 2 5 5 70 92 50 85 80 76 PMC(Si)I11 4-bromotolueno Tx/THF 65 15 86 PMC(S1)112 4-bromotolueno Tx/THF 65 15 100 PMC(Si)I13 4-bromotolueno Tx/THF 65 15 100 2e'f PMC(S1)111 4-clorotolueno Tx/THF 80 30 51 PMC(S1)112 4-clorotolueno Tx/THF 80 30 77 PMC(S1)113 4-clorotolueno Tx/THF 80 30 68 PMC(A)I11 4-bromotolueno Tx/THF 65 15 91 PMC(A)II2 4-bromotolueno Tx/THF 65 15 100 3e,f PMC(A)II3 4-bromotolueno TilTHF 65 15 100 PMC(S1)111 4-clorotolueno Tx/THF 80 30 56 PMC(A)II2 4-clorotolueno Tx/THF 80 30 82 PMC(A)II3 4-clorotolueno Tx/THF 80 30 72 PMC(A)III4 4-bromotolueno Tx/THF 65 20 100 4e'f PMC(A)III4 4-clorotolueno Tx/THF 80 48 100 Frente al acido fenilboronico. Tx/Et0H (1:4), Tx/THF (9:1). Tx = disoluciOn de Trit&in" X405 en agua al Determinado por cromatografia de gases con detector FID. Reproducibilidad ±3%. Carga metalica: 0,05 mol% [Pd]. e Carga metalica: 0,024 mol% [Pd]. f Conversion total a las 30 h con 4-bromotolueno con las PMC(S1)111 y PMC(A)111, a las 82 h con 4-clorotolueno con las PMC(Si)112 y3 y PMC(A)I13 y 3, y a las de 90 h con las PMC(Si)111 y PMC(A)II. 5 m) ensayar de las PMCs de esta invenciOn en reacciones de Heck-Mizoroki entre una olefina, preferentemente un acrilato con haluros de arilo, preferentemente 4- yodotolueno, a temperatura suave (5 90 °C), en un medio organico-acuoso agitado mecanicamente a velocidad constant() en presencia de pequenas cantidades de 10 surfactantes no ionicos con balance hidrofilico-hidrofobico alto (HLB > 15, usados por 17
debajo de su concentracien micelar critica) y con cargas bajas de paladio (0,024— 0,050 mol% [Pd], con respecto del haloareno usado como el sustrato limitante). La Tabla 4 recoge los resultados obtenidos con las PMCs especialmente preferidas. Tabla 4. Resultados en la reacciOn de Heck-Mizoroki con las PMCs de los ejemplos. entrada precursor sustratoa medioD T(°C) t(h) Conversion (%)a PMC(S1)11 4-yodotolueno Tx/THF 90 8 100 1d PMC(Si)I2 4-yodotolueno Tx/THF 90 6 100 PMC(Si)I3 4-yodotolueno Tx/THF 90 7 100 PMC(Si)111 4-yodotolueno Tx/THF 90 20 100 2e PMC(Si)112 4-yodotolueno Tx/THE 90 12 100 PMC(Si)113 4-yodotolueno Tx/THF 90 15 100 PMC(A)II1 4-yodotolueno Tx/THF 90 20 100 3e PMC(A)II2 4-yodotolueno Tx/THF 90 10 100 PMC(A)II3 4-yodotolueno TX/THE 90 15 100 4e PMC(A)III4 4-yodotolueno Tx/THF 90 15 100 a Frente al acrilato de metilo. Tx/THF (9:1). Tx = disolucion de TritOnTM X405 en agua al Determinado por cromatografia de gases con detector FID. Reproducibilidad ±3%. d Carga metalica: 0,05 mol% [Pd]. °Carp metalica: 0,024 mol% [Pd]. 5 n) evaluar la reciclabilidad de las PMCs de esta invencion, mediante la secuencia separacien-lavados-reutilizacion, en las reacciones de Suzuki-Miyaura que se han definido anteriormente en los ensayos de actividad l), comparando los perfiles cineticos de las reacciones sucesivas de cada serie de reciclados. Concretamente se han realizado doce reciclados sucesivos de cada catalizador (13 usos contando la 10 reaccion inicial o reciclado numerado como 0) separando las PMCs utilizando un iman externo y decantando de las disoluciones. Una seleccion de representaciones graficas de algunos perfiles para algunas de las PMCs especialmente preferidas, es la que se muestra a continuacion: 15 Perfil de la reacciOn de Suzuki-Miyaura inicial (0) y de los reciclados primero (1), segundo (2) y duodecimo (12) para PMC(S1)112 con: a) 4-bromotolueno y b) 4- clorotolueno: 18
80 c 60 :o > 40 20 (0) (1) (2) (12) 3 6 15 0 5 10 15 20 25 Tiempo de reaccion (h) 30 Perfil de la reacciOn de Suzuki-Miyaura inicial (0) y de los reciclados primero (1), segundo (2) y duodecimo (12) para PMC(A)II3 con: a) 4-bromotolueno y b) 4- 5 clorotolueno: 3 6 9 12 15 Tiempo de reaccion (h) b) 100 . 0 5 10 15 20 25 Tiempo de reaccion (h) 30 Perfil de la reacci6n de Suzuki-Miyaura inicial (0) y de los reciclados primero (1), segundo (2) y duodecimo (12) para PMC(A)III4 con: a) 4-bromotolueno y b) 4- 10 clorotolueno: a) loo 80 60 40 20 5 10 15 20 Tiempo de reacci6n (h) 19 b) loo 80 C 60 1.0 8 16 24 Tiempo de reaccion (h) 32 40 48
o) evaluar la reciclabilidad de las PMCs de esta invenciOn, mediante la secuencia separaciOn-lavados-reutilizaciOn, en las reacciones de Heck-Mizoroki que se han definido anteriormente en los ensayos de actividad m), comparando los perfiles 5 cineticos de las reacciones sucesivas de cada serie de reciclados. Concretamente se han realizado doce reciclados sucesivos de cada catalizador (13 usos contando la reacci6n inicial o reciclado numerado como 0) separando las PMCs utilizando un iman externo y decantando de las disoluciones. Una seleccion de representaciones graficas de algunos perfiles para algunas de las PMCs especialmente preferidas, es 10 la que se muestra a continuaciOn: 15 Perfil de la reacci6n de Heck-Mizoroki inicial (0) y de los reciclados primero (1), segundo (2) y duodecimo (12) con 4-yodotolueno para: a) PMC(S1)13 y b) PMC(S1)112: 1 2 3 4 5 6 7 Tiempo de reacci6n (h) 2 4 6 8 10 Tiempo de reacci6n (h) 12 Perfil de la reacciOn de Heck-Mizoroki inicial (0) y de los reciclados primero (1), segundo (2) y duodecimo (12) PMC(A)II14: a) 100 (2) 80 con 4-yodotolueno para: a) PMC(A)II3 y b) 5 10 Tiempo de reacciem (h) .5 20 5 10 Tiempo de reaccian (h) 15
p) cuantificar el posible lixiviado de paladio de las PMCs de esta invencion, mediante analisis elemental cuantitativo de paladio (ICP-MS), tanto de las disoluciones separadas en cada uso consecutivo como de las PMCs al final de cada serie de 5 reciclados en las reacciones de Suzuki-Miyaura que se han definido anteriormente en los ensayos de actividad l), correlacionando el eventual lixiviado de las PMCs con los ligeros descensos de las conversiones (medidas en cada caso siempre a un mismo tiempo) en las reacciones sucesivas en cada serie de los ensayos que se han definido anteriormente en la evaluaciOn n). La Tabla 5 recoge una selecciOn 10 ilustrativa de estas correlaciones en este tipo de acoplamiento para algunas de las PMCs especialmente preferidas. Tabla 5. Descenso de conversion y lixiviado de paladio en los reciclados, y % total del metal encontrado en las disoluciones y perdido por las PMCs en reacciones de Suzuki-Miyaura. precursor reciclado N°: 0-1 1.2 2-3 3-11 12 total perdido por las PMCe descenso de PMC(Si)112` conver. en %a 0 I) 0 9 2 11 %Pd lixiviadob 1,2 0,0 0,2 7,2 0,4 9 n.d. descenso de PMC(Si)112d conver. en %a 5 0 0 11 1 17 %Pd lixiviadob 3,8 0,5 0,3 13,0 0,4 18 19 descenso de PMC(A)I13c conver. en °/08 0 0 0 7 3 10 %Pd lixiviadob 0,0 0,0 0,0 6,4 2,6 9 8 descenso de PMC(A)I13d conver. en %a 3 0 0 8 2 13 %Pd lixiviadob 4,6 0 0 6,8 2,6 14 n.d. descenso de PMC(A)II14c conver. en %a 0 0 0 0 0 0 %Pd lixiviadob 0,0 0,0 0,0 0,2 0,0 0,2 n.d. descenso de PMC(A)II14d conver. en %a 0 0 0 4 5 9 %Pd lixiviadob 0,1 0,1 0,0 0,5 0,2 0,9 1,5 a Determinadas por cromatografia de gases con delector FID. Reproduabilidad ±3%. b Determined° por Desviaciones Estandar Relatives en las cuantificaciones 5 10%. Con 4-bromotolueno; medidas a las 15 h para PMC(Si)112 y PMC(A)II3, y a las 20 h para PMC(A)II14. 21
° Con 4-clorotolueno; medidas a las 30 h para PMC(S1)112 y PMC(A)II3, y a las 48 h para PMC(A)II14. e Medido por ICP-MS sabre las propias PMCs tras trece usos; n.d. = No determinado. q) cuantificar el posible lixiviado de paladio de las PMCs de esta invencion, mediante analisis elemental cuantitativo de paladio (ICP-MS), tanto de las disoluciones separadas en cada uso consecutivo como de las PMCs al final cada serie de 5 reciclados en las reacciones de Heck-Mizoroky que se han definido anteriormente en los ensayos de actividad m), correlacionando el eventual lixiviado de las PMCs con los ligeros descensos de las conversiones (medidas en cada caso siempre a un mismo tiempo) en las reacciones sucesivas en cada serie de los ensayos que se han definido anteriormente en la evaluaciOn o). La Tabla 6 recoge una selecciOn 10 ilustrativa de estas correlaciones en este tipo de acoplamiento para algunas de las PMCs especialmente preferidas. Tabla 6. Descenso de conversion y lixiviado de paladio en los reciclados, y % total del metal encontrado en las disoluciones y perdido por las PMCs en reacciones de Heck-Mizoroky. a Determinadas perdido por precursor reciclado N°: 0-1 1-2 2-3 3-11 12 total las PMCs d descenso de PMC(Si)13b conver. en %a 0 0 0 9 2 11 %Pd lixiviadob 1,9 0,9 0,9 8,0 1,3 13 n.d. descenso de PMC(Si)112c conver. en %a 0 0 0 8 1 9 %Pd lixiviadob 0,8 0,0 0,2 6,9 1,1 9 11 descenso de PMC(A)I13c conver. en %a 0 0 0 4 1 5 %Pd lixiviadob 0,5 0,3 0,1 3,1 1,0 5 7 descenso de PMC(A)1114` conver. en %a 0 0 0 0 0 0 %Pd lixiviadob 0,0 0,0 0,0 0,02 0,0 0,02 0,18 par cromatografia de gases con detector FID. Reproducibilidad ±3%. b Determinado par ICP-MS. Desviaciones Estandar Relatives en las cuantificaciones s 10%. Medidas a las 7 h para PMC(Si)I3, a las 12 h pare PMC(Si)112 y a las 15 h para PMC(A)II3 y PMC(A)II14. d Medido par ICP-MS sabre las propias PMCs tras trece usos; n.d. = No determined°. r) determinar los valores de productividad (TON° o "turnover number" en primer uso del 15 catalizador) y de actividad (TOF0 o "turnover frequency" en el primer uso del 22
catalizador) de las PMCs de esta invenciOn en las reacciones iniciales de Suzuki-Miyaura que se han definido anteriormente en los ensayos de actividad I), asi como el TON acumulado (TONT) y el TOF promedio (TOFAv) en cada serie de usos consecutivos que se han descrito anteriormente en la evaluaciOn n), junto al 5 contenido de paladio encontrado en los productos cuya determinaciOn se describe en las cuantificaciones p). La Tabla 7 y la Tabla 8 recogen los valores encontrados en las reacciones de Suzuki-Miyaura para algunas de las PMCs especialmente preferidas de esta invenciOn. 10 Tabla 7. Valores de TOF y TON mostrados par algunas PMCs de los ejemplos en la reaccion de Suzuki-Miyaura con 4-bromotolueno y el contenido metalico encontrado en los productos. TON TOFAv TON— TOFA,, Contenido precursor TONob TONTG (h-l)b 01-1)c (11-1) Pd (ppm)d PMC(Si)111 3584 239 42128 216 23 3 PMC(Si)112 4167 278 52046 267 11 1 PMC(Si)113 4167 278 52088 267 11 2 PMC(A)II1 3792 253 43624 224 29 3 PMC(A)1I2 4167 278 53046 272 6 1 PMC(A)113 4167 278 52629 270 9 1 PMC(A)1114 4167 208 53879 207 1 0,023 a Tiempos de reaccion: 20 h para PMC(A)III4, 15 h para el resto Valor en la reaccion inicial. Valor en los trece usos del catalizador. d Contaminacion por paladio del producto en partes por milk:0 en masa. Tabla 8. Valores de TOF y TON mostrados par algunas PMCs de los ejemplos en la reaccion de Suzuki-Miyaura con 4-clorotolueno y el contenido metalico encontrado en los productos. TON TOFAv TON — TOFA, Contenido precursor TONob TONT` (11-1)b (h-1)` (h-1) Pd (ppm)d PMC(Si)I11 2125 71 22085 57 14 10 PMC(Si)112 3209 107 3650:3 94 13 3 PMC(S1)113 2834 94 32128 82 12 3 PMC(A)II1 2334 78 25210 65 13 7 PMC(A)I12 3417 114 39211 101 13 2 PMC(A)I13 3042 101 36545 94 7 2 PMC(A)1114 4167 87 53254 85 2 0,107 23
a Tiempos de reaccion: 48 h para PMC(A)III4, 30 h para el resto b Valor en la reaccion inicial. Valor en los trece usos del catalizador. d Contaminacidn por paladio del product° en partes por mill& en masa. s) determinar los valores de productividad (TON() o "turnover number" en primer uso del catalizador) y de actividad (TOF0 o 'turnover frequency" en el primer uso del catalizador) de las PMCs de esta invenciOn en las reacciones iniciales de Heck-5 Mizoroki que se han definido anteriormente en los ensayos de actividad m), asi como el TON acumulado (TONT) y el TOF promedio (TOFA,) en cada serie de usos consecutivos que se han descrito anteriormente en la evaluaciOn o), junto al contenido de paladio encontrado en los productos cuya determinaci6n se describe en las cuantificaciones q). La Tabla 9 recoge los valores encontrados en las reacciones 10 de Heck-Mizoroki para las PMCs de los ejemplos de esta invencion. Tabla 9. Valores de TOF y TON mostrados por las PMCs de los ejemplos en la reacciOn de Heck-Mizoroki con 4-yodotolueno y el contenido metalico encontrado en los productos. precursor TONob TON (11-1)b TONT` TOFAv (h-1)` TOF0 — TOFA, (11-1) Contenido Pd (ppm)d PMC(S1)11 2000 250 24400 235 15 5 PMC(Si)I2 2000 333 25100 322 11 4 PMC(S1)13 2000 286 25260 278 8 3 PMC(Si)II1 4167 208 52421 202 6 2 PMC(Si)112 4167 347 52963 340 7 1 PMC(Si)113 4167 278 53254 273 5 1 PMC(A)II1 4167 208 52921 204 4 2 PMC(A)112 4167 417 53463 411 6 1 PMC(A)1I3 4167 278 53504 274 4 1 PMC(A)1I14 4167 278 53963 277 1 0,002 Tiempos de reacciOn: 8 (PMC(Si)11), 6 (PMC(Si)12), 7 (PMC(Si)13), 20 (PMC(S0111 y PMC(A)II1), 12 (PMC(Si)I12), 10 (PMC(A)I12) y 15 h (PMC(Si)I13, PMC(A)II3 y PMC(A)II14. b Valor en la reacciOn inicial. Valor en los trece usos del catalizador. d ContaminaciOn por paladio del producto en partes por mill& en masa. t) adicional y finalmente, analizar las imagenes TEM (Microscopia Electronica de 15 TransmisiOn) de las PMCs, tanto antes de su uso en las reacciones que se han 24
definido anteriormente en los ensayos de actividad I) y m) como al finalizar las series de reciclados que se han definido anteriormente en las evaluaciones n) y o), asi como de muestras preparadas a partir de las disoluciones separadas en cada reacciOn, comprobando que las PMCs no sufren cambios morfologicos apreciables y 5 que no se observan agregados de paladio metalico junto a ellas ni en las muestras preparadas a partir de las disoluciones separadas con los productos al final de cada reacciOn. 10 15 DESCRIPCIoN DE LOS DIBUJOS Figura 1. Representaci6n esquematica de la heterogeneizacion de los CPs para dar las PMCs objeto de la presente invenciOn. Figura 2. Representacion esquernatica de los CPs objeto de la presente invenciOn. Figura 3. Esquema de sintesis de los nuevos CPs de los tipos I, II y III y de sus precursores. Figura 4. Perfil de la reacci6n de Suzuki-Miyaura inicial (0) y de los reciclados primero 20 (1), segundo (2) y duodecimo (12) para PMC(S1)112 con: a) 4-bromotolueno y b) 4-clorotolueno. Figura 5. Perfil de la reacciOn de Suzuki-Miyaura inicial (0) y de los reciclados primero (1), segundo (2) y duodecimo (12) para PMC(A)II3 con: a) 4-bromotolueno y b) 25 4-clorotolueno. 30 Figura 6. Perfil de la reacciOn de Suzuki-Miyaura inicial (0) y de los reciclados primero (1), segundo (2) y duodecimo (12) para PMC(A)III4 con: a) 4-bromotolueno y b) 4-clorotolueno. Figura 7. Perfil de la reacciOn de Heck-Mizoroki inicial (0) y de los reciclados primero (1), segundo (2) y duodecimo (12) con 4-yodotolueno para: a) PMC(S1)13 y b) PMC(S1)112. 35 Figura 8. Perfil de la reacciOn de Heck-Mizoroki inicial (0) y de los reciclados primero (1), segundo (2) y duodecimo (12) con 4-yodotolueno para: a) PMC(A)II3 y b) 25
PMC(A)II14. MODO DE REALIZACION DE LA INVENCION 5 La presente invenciOn se ilustra adicionalnlente con los siguientes ejemplos ilustrativos, aunque no limitantes, en los que se indican procedimientos experimentales, datos espectroscOpicos y analiticos de complejos de paladio y de sus precursores y de particulas magneticas con los complejos soportados, asi como de ensayos cataliticos con 10 las mismas. Ejemplo 1. Preparacion de la sal de imidazolio 1.1. En una ampolla de 100 mL, dotada con una valvula de punzem de tefle)n, se coloco el N-15 metilimidazol (0,65 g, 7,8 mmol) y la N-(2-Bromoetil)ftalimida (1,00 g, 3,9 mmol), en unos 40 mL de THF y se calento con agitacion hasta 80 °C. Tras 16 h se observO la presencia de un precipitado blanco que, tras filtrar, se lave) con hexano (2 x 10 mL) para eliminar el exceso de N-metilimidazol y se sece) a vacio. Se obtuvo el producto 1.1 como un sOlido blanco (1,18 g, 90%). Anal. Calc. para C14H1402N3Br.H20 (354,20): C, 47,47; H, 4,55; N, 20 11,86%. Encontrado: C, 47,42; H, 4,24; N, 11,93%. RMN 1H (CDCI3, 300 MHz): ô4,06 (s, 3H, Imz-Me), 4,23 (t, 3.4th = 5,4 Hz, 2H, CH2ftal), 4,79 (t, 34,H = 5,4 Hz, 2H, CH2Innz), 7,25 y 7,26 (2 x s, 2 x 1H, Imz-H4y H5), 7,73 (m, 2H, o-ftal), 7,80 (m, 2H, m-ftal), 10,57 (s, 1H, Imz-H2). RMN 13C{1H} (CDCI3, 75 MHz): 6 35,3 (CH2ftal), 37,5 (lmz-Me), 47,4 (CH2Imz), 122,4 y 123,1 (Imz-C4 y C5), 122,7 (o-ftal), 131,0 (ipso-ftal), 134,1 (m-ftal), 136,6 (Imz-C2), 25 167,2 (C=0). MS (ESI+/TOF, CH2C12/Me0H/NH4HCOO 5 mM): m/z 256,1092 [M - Br]. 30 1.1 Ejemplo 2. Preparacion de la sal de imidazolio 1.2. El compuesto 1.2 se prepare) de forma similar a la descrita para la sal 1.1 del Ejemplo 1, partiendo de N-mesitilimidazol (0,50 g, 2,7 mmol) y N-(2-bromoetil)ftalimida (0,34 g, 1,4 26
mmol), en THF (40 mL), a 90 °C y durante 16 h. Se obtuvo el compuesto 1.2 coma un solid° aceitado de color blanco (0,56 g, 95%). Anal. Calc. para C22H2202N3Br (440,34): C, 60,01; H, 5,04; N, 9,54%. Encontrado: C, 59,75; H, 5,06; N, 9,47%. RMN 1H (CDCI3, 300 MHz): 6 2,09 (s, 6H, Mes-o-Me), 2,31 (s, 3H, Mes-p-Me), 4,33 (t, JH,H= 5,0 Hz, 2H, 5 CH2ftal), 5,14 (t, 34,H = 5,0 Hz, 2H, CH2Imz), 6,97 (s, 2H, m-Mes), 7,04 y 7,51 (2 x t, = 1,9 Hz, 2 x 1H, Imz-H4 y H5), 7,73 (m, 2H, o-ftal), 7,78 (m, 2H, m-ftal), 10,50 (t, 3JH,H = 1,9 Hz, 1H, Imz-H2). RMN 13C{1H} (CDCI3, 75 MHz): 617,6 (Mes-p-Me), 21,1 (Mes-o-Me), 39,0 (CH2ftal), 49,6 (CH2Imz), 122,8 y 123,0 (Imz-C4 y C5), 123,7 (o-ftal), 129,9 (m-Mes), 130,6 (ipso-Mes), 131,5 (ipso-ftal), 134,4 (o-Mes), 134,5 (m-ftal), 138,8 (Imz-C2), 141,4 (p-10 Mes), 167,2 (C=0). MS (ESI+/TOF, CH2C12/Me0H/NR4HCOO 5 mM): m/z 360,1711 [M - Br]. 1.2 15 Ejemplo 3. Preparacion de la sal de imidazolio 1.3. El compuesto 1.3 se prepar6 de forma similar a la descrita para la sal 1.1 del Ejemplo 1, partiendo de N-(2,6-diisopropilfenil)imidazol (0,50 g, 2,2 mmol) y N-(2-bromoetil)ftalimida (0,28 g, 1,1 mmol), en THF (40 mL), a 90°C y durante 16 h. Se obtuvo el compuesto 1.3 20 como un sOlido blanco aceitoso (0,48 g, 90%). Anal. Cale. para C25H2802N3Br.1,2H20 (505,04): C, 59,57; H, 6,08; N, 8,34%. Encontrado: C, 59,96; H, 5,95; N, 7,92%. RMN 1H (CDCI3, 300 MHz): 61,11 (d, 34,H = 7,0 Hz, 6H, CH(CH3)2), 1,23 (d, JH,H = 7,0 Hz, 6H, CH(CH3)2), 1,83 (sep, 3JH,H = 7,0 Hz, 2H, CH(CH3)2), 4,35 (t, 3JH,H = 5,2 Hz, 2H, CH2ftal), 5,22 (t, 3JKH = 5,2 Hz, 2H, CH2Imz), 7,03 y 7,58 (2 x s, 2 x 1H, Imz-H4 y H5), 7,04 (d, 25 = 7,9 Hz, 2H, m-Ph), 7,51 (t, JH,H = 7,9 Hz, 1H, p-Ph), 7,73 (m, 2H, o-ftal), 7,80 (m, 2H, m-ftal), 10,51 (s ancho, 1H, Imz-H2). RMN 13C{1H} (CDCI3, 75 MHz): 6 24,3 (CH(CH3)2), 24,5 ( CH(CH3)2), 28,5 (CH(CH3)2), 39,2 (CH2ftal), 49,7 (CH2Imz), 123,0 y 123,8 (Imz-C4 y C5), 123,6 (m-Ph), 124,7 (o-ftal), 130,1 (ipso-Ph), 131,6 (ipso-ftal), 131,9 (o-Ph), 134,5 (m-ftal), 138,9 (Imz-C2), 145,5 (p-Ph), 167,7 (C=0). MS (ESI+/TOF, CH2C12/Me0H/NH4HCOO 30 5 mM): miz 402,2176 [M - Br]. 27
0 1c Ejemplo 4. Preparacion de la sal de imidazolio 2(51)1. 5 En una ampolla de 50 mL con (3-bromopropil)trietoxisilano (0,29 g, 1,0 mmol), se hizo vacio durante 10 min y se ariadieron 2 mL de CH3CN seco. A continuaci6n se adicionO el N-metilimidazol (0,08 g, 1,0 mmol). La disolucion amarilla resultante se dejO con agitaciOn a 100 °C durante 16 h, para despues evaporar el disolvente. El aceite amarillo resultante se lavo con hexano (2 x 15 mL), obteniendose el compuesto 2(51)1 como un aceite 10 amarillo (0,33 g, 89%). Anal. Calc. para C13H2703N2SiBr (367,36): C, 42,50; H, 7,41; N, 7,62%. Encontrado: C, 42,00; H, 6,85; N, 8,04%. RMN 1H (CDCI3, 300 MHz): 6 0,52 (t, = 8,5 Hz, 2H, SiCH2), 1,12 (t, 3s/H,H = 7,0 Hz, 9H, CH3CH20), 1,93 (m, 2H, SiCH2CH2), 3,72 (c, 3JH,H = 7,0 Hz, 6H, CH3CH20), 4,04 (s, 3H, lmz-Me), 4,24 (t, 3AH = 7,2 Hz, 2H, CH2Imz), 7,31 y 7,57 (2 x t, 341,H = 1,6 Hz, 2 x 1H, Imz-H4 y H5), 10,2 (s, 1H, Imz-H2). 15 RMN 13C{1H} (CDCI3, 75 MHz): 6 7,0 (SiCH2), 18,2 (CH3CH20), 24,3 (S1CH2CH2), 36,6 (lmz-Me), 51,6 (CH2Imz), 58,5 (CH3CH20), 121,7 y 123,5 (Imz-C4 y C5), 137,4 (Imz-C2). MS (ESIF/TOF, CH2C12/Me0H/NH4HCOO 5 mM): tniz 247,1780 [M - Br]. 20 Br-2(Si)1 Ejemplo 5. Preparacion de la sal de imidazolio 2(Si)2. El compuesto 2(51)2 se preparO de forma similar a la descrita para la sal 2(51)1 del Ejemplo 4, partiendo de N-mesitilimidazol (0,22 g, 1,2 mnnol) y el derivado bromado (0,34 25 g, 1,2 mmol), en CH3CN (2,5 mL), a 100 °C y durante 24 h. Todos los reactivos sOlidos se mantuvieron previamente a vacio durante 10 min. Se obtuvo el compuesto 2(51)2 como un sOlido blanco aceitado (0,55 g, 98%). Anal. Calc. para C211-13503N2SiBr.0,1H20 (489,530): C, 53,29; H, 7,50; N, 5,92%. Encontrado: C, 52,77; H, 7,12; N, 6,46%. RMN 1H (CDCI3, 300 MHz): 60,62 (m, 2H, SiCH2), 1,18 (t, 3JitH = 7,0 Hz, 9H, CH3CH20), 2,04 (s, 28
6H, Mes-o-Me), 2,07 (m, 2H, SiCH2CH2), 2,30 (s, 3H, Mes-p-Me), 3,80 (c, 3JH,H = 7,0 Hz, 6H, CH3CH20), 4,72 (t, 3JH,H = 7,0 Hz, 2H, CH2Imz), 6,96 (s, 2H, m-Mes), 7,15 y 7,67 (2 x t, 34,H = 1,5 Hz, 2 x 1H, Imz-H4 y H5), 10,4 (s ancho, 1H, Imz-H2). RMN 13C{1H} (CDCI3, 75 MHz): 6 6,8 (SiCH2), 17,6 (Mes-o-Me), 18,2 (CH3CH20), 21,0 (Mes-p-Me), 24,5 5 (S1CH2CH2), 52,0 (CH2Imz), 58,6 (CH3CH20), 122,7 y 122,9 (Imz-C4y C5), 129,8 (m-Mes), 130,6 (ipso-Mes), 134,1 (o-Mes), 138,2 (Imz-C4), 141,2 (p-Mes). MS (ESI+/TOF, CH2C12/Me0H/NH4HCOO 5 mM): m/z 391,2412 [M - Br]. 10 (Et0)3Si.,,N•It•N Br-2(Si)2 Ejemplo 6. Preparacion de la sal de imidazolio 2(Si)3. El compuesto 2(S1)3 se prepar6 de forma similar a la descrita para la sal 2(Si)1 del Ejemplo 4, partiendo de N-(2,6-diisopropilfenil)imidazol (0,28 g, 1,2 mmol) y el derivado 15 bromado (0,34 g, 1,2 mmol), en CH3CN (2,5 mL), a 100 °C y durante 24 h. Todos los reactivos sOlidos se tuvieron a vacio durante 10 min antes de su utilizaciOn. Se obtuvo el compuesto 2(Si)3 como un sOlido blanco de aspecto aceitoso (0,61 g, 99%). Anal. Calc. para C24H4103N2SiBr-(2,4CH3CN y 2C3H60) (728,28): C, 57,52; H, 8,03; N, 7,62%. Encontrado: C, 57,91; H, 8,03; N, 7,27%. RMN 1H (CDCI3, 300 MHz): ô0,61 (t, 3JKH = 7,7 20 Hz, 2H, S1CH2), 1,13 (d, 3JH,H = 7,2 Hz, 6H, CH(CH3)2), 1,18 (t, 3JH,H = 7,0 Hz, 9H, CH3CH20), 1,20 (d, 34,H = 7,2 Hz, 6H, CH(CH3)2), 2,07 (m, 3JH,H = 7,7 Hz, 2H SiCH2CH2), 2,25 (sep,3JH,H = 7,2 Hz, 6H, CH(CH3)2), 3,78 (c, 3JH,H = 7,0 Hz, 6H, CH3CH20), 4,78 (t, 3,41,H = 7,7 Hz, 2H, CH2Imz), 7,18 y 7,88 ( 2 x s ancho, 2 x 1H, Imz-H4 y H5), 7,27 (d, 2H, 34H = 7,6 Hz, m-Ph), 7,49 (t, 1H, 3JH,H = 7,6 Hz,p-Ph), 10,3 (s, 1H, Imz-H2). RMN 13C{1H} 25 (CDCI3, 75 MHz): 6 6,6 (SiCH2), 18,2 (CH3CH20), 24,0 (CH(CH3)2), 24,3 (CH(CH3)2), 24,5 (S1CH2CH2), 28,6 (CH(CH3)2), 52,0 (CH2Imz), 58,5 (CH3CH20), 123,0 y 124,0 (Imz-C4 y C5), 124,6 (m-Ph), 130,0 (ipso-Ph), 131,8 (C6H3(o-Ph), 138,2 (Imz-C2), 145,2 (p-Ph). MS (ESI+/TOF, CH2C12/Me0H/NH4HCOO 5 mM): miz 433,2881 [M - 29
2(Si)3 Ejemplo 7. Preparaci6n de la sal de imidazolio 2(A)1. 5 Se adicione) hidrazina (2,10 mL, 43,1 mmol) a una ampolla de 50 mL con la sal de imidazolio 1.1 descrita en el Ejemplo 1 (1,40 g, 4,3 mmol) en 25 mL de 2-propanol y se calento a 40 °C durante una noche. La suspension blanca inicial se tome) a una disolucion transparente con el avance de la reaccion para finalmente, precipitar un sOlido blanco que se corresponde con el subproducto de la desprotecciOn, la ftalilhidrazina. La mezcla se 10 enfrio, filtro y evaporO obteniendose el producto deseado 2(A)1 como un aceite amarillo (0,80 g, 95%). Anal. Calc. para C6H12N2Br (206,08): C, 34,97; H, 5,87; N, 20,39%; Encontrado: C, 34,31; H, 5,98; N, 19,89%. RMN 1H (CDCI3, 300 MHz): ö 3,19 (t, 3J11,H = 5,6 Hz, 2H, NH2CH2), 4,05 (s, 3H, lmz-Me), 4,44 (t, 3,40.1 = 5,6 Hz, 2H, CH2Imz), 7,27 y 7,49 (2 x s, 2 x 1H, Imz-H4 y H5), 10,33 (s, 1H, Imz-H2). RMN 13C{1H} (CDCI3, 75 MHz): 6 15 36,7 (NH2CH2), 41,4 (lmz-Me), 52,3 (CH2Imz), 122,3 y 122,5 (Imz-C4 y C5), 138,6 (Imz-C2). MS (ESI+/TOF, CH2C12/Me0H/NH4HCOO 5 mM): miz 126,1026 [M - Br]. m Br-2(A)1 20 Ejemplo 8. Preparacion de la sal de imidazolio 2(A)2. El compuesto 2(A)2 se prepare) de forma similar a la descrita para la sal 2(A)1 del Ejemplo 7, partiendo de la sal de imidazolio 1.2 descrita en el Ejemplo 2 (1,29 g, 2,9 mmol) e hidrazina (1,43 mL, 29,0 mmol), en isopropanol, a 40 °C y durante una noche. 25 Tras filtrar, evaporar y lavar con hexano se obtuvo la sal de imidazolio 2(A)2 como un aceite amarillo (0,87 g, 95%). Anal. Calc. para C14H20N3Br.0,7H20 (322,84): C, 52,08; H, 6,68; N, 13,02%; Encontrado: C, 51,82; H, 6,34; N, 13,24%. RMN 1H (CDCI3, 300 MHz): 6 2,05 (s, 6H, Mes-o-Me), 2,31 (s, 3H, Mes-p-Me), 3,23 (t, 3JH,H = 5,6 Hz, 2H, NH2CH2), 4,81 (t, 3JKH = 5,6 Hz, 2H, CH2Imz), 6,97 (s, 2H, in-Mes), 7,11 y 7,91 (2 x t, 3JH,H = 1,7 Hz, 2 x 30
5 1H, Imz-H4 y H5), 10,09 (t, 34,H = 1,7 Hz, 1H, Imz-H2). RMN 13C{1H} (CDCI3, 75 MHz): 6 17,8 (Mes-p-Me), 21,0 (Mes-o-Me), 40,9 (NH2CH2), 50,3 (CH2Imz), 123,0 y 124,0 (Imz-C4 y C5), 129,7 (m-Mes), 130,7 (ipso-Mes), 134,4 (o-Mes), 137,9 (Imz-C2), 141,0 (p-Mes). MS (ESI+/TOF, CH2C12/Me0H/NH4FICOO 5 mM): m/z 230,1652 [M - H2NZ2N Br 2(A)2 Ejemplo 9. Preparacion de la sal de imidazolio 2(A)3. 10 El compuesto 2(A)3 se prepar6 de forma similar a la descrita para la sal 2(A)1 del Ejemplo 7, partiendo de la sal de imidazolio 1.3 descrita en el Ejemplo 3 (0,46 mL, 9,50 mmol) e hidrazina (0,46 mL, 9,50 mmol), en isopropanol, a 40 °C y durante una noche. Tras filtrar, evaporar y lavar con hexano se obtuvo la sal de imidazolio 2(A)2 como un aceite amarillo (0,31 g, 92%). Anal. Calc. para C17H26N3Br-0,4H20: C, 56,79; H, 7,51; N, 15 11,69%; Encontrado: C, 57,07; H, 7,98; N, 12,13%. RMN 1H (CDCI3, 300 MHz): (51,17 (d, 3JKH = 6,9 Hz, 12H, CH(CH3)2), 2,31 (sep., 34H = 6,9 Hz, 2H, CH(CH3)2), 3,22 (t, 34H = 5,4 Hz, 2H, NH2CH2), 4,87 (t, 34tH = 5,4 Hz, 2H, CH2Imz), 7,12 y 7,58 (2 x t, 3,41,H = 1,3 Hz, 2 x 1H, Imz-H4 y H5), 7,28 (d, 3.41,H = 7,9 Hz, 2H, m-Ph), 7,52 (t, 3JKH = 7,9 Hz, 1H, p-Ph), 10,51 (t, 3JKH = 1,3 Hz, 1H, Imz-H2). RMN 13C{1H} (CDCI3, 75 MHz): (5 24,1 20 (CH(CH3)2), 24,4 (CH(CH3)2), 28,6 (CH(CH3)2), 41,6 (NH2CH2), 51,6 (CH2Imz), 123,2 y 123,5 (Imz-C4 y C5), 124,7 (m-Ph), 130,1 (ipso-Ph), 131,9 (o-Ph), 139,0 (Imz-C2), 145,5 (p-Ph). MS (ESIIITOF, CH2C12/Me0H/NH4HCOO 5 mM): m/z 272,2082 [M - Br]. 25 2(A)3 Ejemplo 10. Preparacion del complejo de paladio l(Si)1. Se pesaron en una ampolla bajo argon la sal de imidazolio 2(Si)1 descrita en el Ejemplo 4 (0,58 g, 1,6 mmol), cloruro de paladio (0,28 g, 1,6 mmol), carbonato de potasio (1,09 g, 31
7,9 mmol) y yoduro de sodio (1,66 g, 11,1 mmol), y se pusieron en un desecador Buchi a 10 mbar y 95 °C durante 24 h. Posteriormente, se anadieron 12 mL de 4-picolina, tratada previamente con moleculas shieves durante una noche, formandose una suspensi6n rojiza que se dejo agitando a 80 °C durante 24 h bajo arg6n. Tras evaporar la 4-picolina, 5 se extrajo con CHCI3, se filtro la disoluciOn y se ariadio hexano para eliminar restos de haluro de paladio. Tras filtrar y evaporar el disolvente se obtuvo el complejo 1(Si)I como un solid° pulverulento de color amarillo (1,12 g, 96%). Anal. Calc. para C19H3303N312S1Pd (739,80): C, 30,85; H, 4,50; N, 5,68%. Encontrado: C, 30,36; H, 4,40; N, 5,93%. RMN 1H (CDCI3, 300 MHz): 6 0,73 (t, 3JH,H = 8,0 Hz, 2H, S1CH2), 1,21 (t, 34H = 7,0 Hz, 9H, 10 CH3CH20), 2,15 (m, 2H, SiCH2CH2), 2,35 (s, 3H, plc-Me), 3,83 (c, 34,H = 7,0 Hz, 6H, CH3CH20), 3,95 (s, 3H, lmz-Me), 4,38 (t, 34,H = 8,0 Hz, 2H, CH2Imz), 6,90 y 6,96 (2 x d, 3,41,11 = 2,0 Hz, 2 x 1H, Imz-H4 y H5), 7,09 (d, 3JH,H = 5,9 Hz, 1H, m-pic), 8,83 (d, 34,H = 5,9 Hz, 1H, o-pic). RMN 13C{1H} (CDCI3, 75 MHz): 67,7 (SiCH2), 18,4 (CH3CH20), 21,1 (pic-Me), 23,1 (SiCH2CH2), 39,2 (lmz-Me), 537 (CH2Imz), 58,6 (CH3CH20), 121,7 y 123,0 15 (Imz-C4 y C5), 125,3 (m-pic), 145,6 (Imz-C2), 149,4 (p-pic), 153,2 (o-pic). IR (KBr): v 3050- 3120 (m, Csp-H st), 1618 (m, C=C st), 1542 (s, C=N st), 1420-1470 (m, arC=C st), 1080 (w, Si-O-C st), 957 (w, Si-O-C st), 806 (m, Si-C st), 687 cm-1 (m, Si-0 st). MS (ESI+/TOF, CH2C12/Me0H/NH4HCOO 5 mM): ink 740,9418 [M + H. 20 (Et0)3SiNN,, I-Pd-I .)\1 I(Si)1 Ejemplo 11. Preparaci6n del complejo de paladio l(Si)2. El compuesto l(Si)2 se prepar6 como se ha descrito para el complejo l(S1)1 del Ejemplo 25 10, partiendo de la sal de imidazolio 2(Si)2 descrita en el Ejemplo 5 (0,57 g, 1,2 mmol), cloruro de paladio (0,21 g, 1,2 mmol), carbonato de potasio (0,83 g, 6,0 mmol) y yoduro de sodio (1,26 g, 8,4 mmol), en 12 mL de 4-picolina, a 100 °C y durante 16 h. Se obtuvo el compuesto l(Si)2 como un solido pulverulento de color naranja (0,99 g, 98%). Anal. Calc. para C27H4103N3I2SiPd (843,95): C, 38,43; H, 4,90; N, 4,98%. Encontrado: C, 38,22; 30 H, 4,78; N, 5,36%. RMN 1H (CDCI3, 300 MHz): 6 0,80 (t, JH,H = 8,2 Hz, 2H, S1CH2), 1,25 (t, 3JRH = 7,0 Hz, 9H, CH3CH20), 2,25 (m, 2H, SiCH2CH2), 2,28 (s, 3H, pic-Me), 2,30 (s, 32
6H, Mes-o-Me), 2,34 (s, 3H, Mes-p-Me), 3,86 (c, 34,F, = 7,0 Hz, 6H, CH3CH20), 4,62 (t, 34,H = 7,0 Hz, 2H, CH2Imz), 6,87 y 7,24 (2 x d, 34,F, = 2,0 Hz, 2 x 1H, Imz-H4 y H5), 6,97 (s, 2H, m-Mes), 6,98 (d, 34,H = 5,6 Hz, 2H, m-plc), 8,53 (d, 34,H = 5,6 Hz, 2H, o-pic). RMN 13C{1H} (CDCI3, 75 MHz): 6 7,7 (SiCH2), 18,4 (CH3CH20), 21,0 (Mes-p-Me), 21,1 (pic-Me), 5 21,7 (Mes-o-Me), 23,3 (SiCH2CH2), 55,0 (CH2Imz), 58,6 (CH3CH20), 121,3 y 136,1 (lmz-y C5), 125,1 (m-plc), 129,4 (m-Mes), 135,0 (ipso-Mes), 139,0 (p-Mes), 148,4 (o-Mes), 149,1 (p-pic), 152,9 (o-pic). IR (KBr): v 3070-3160 (m, arC-H st), 1618 (m, arC=C st), 1531 (s, C=N st), 1400-1480 (m, arC=C st), 1076 (w, Si-O-C st), 956 (w, Si-O-C st), 806 (m, Si-C st), 692 cnri-1 (m, Si-0 st). MS (ESIf/TOF, CH2C12/Me0H/NH4HCOO 5 mM): m/z 10 862,0312 [M + NH4], 845,0154 [M + H], 717,0939 [M - Ir. I(Si)2 Ejemplo 12. Preparacion del complejo de paladio l(Si)3. 15 El compuesto l(Si)3 se preparo de forma similar a la descrita para el complejo 1(51)1 del Ejemplo 10, partiendo de la sal de imidazolio 2(Si)3 descrita en el Ejemplo 6(0,62 g, 1,2 mmol), cloruro de paladio (0,21 g, 1,2 mmol), carbonato de potasio (0,83 g, 6,0 mmol) y yoduro de sodio (1,28 g, 8,4 mmol), en 12 mL de 4-picolina, a 100°C y durante 16 h. Se 20 obtuvo el compuesto 1(51)3 como un &Nick) pulverulento de color naranja (0,99 g, 98%). Anal. Calc. para C30H4703N3I2S1Pd (843,95): C, 40,67; H, 5,35; N, 4,74%. Encontrado: C, 41,03; H, 5,75; N, 5,21%. RMN 1H (CDCI3, 300 MHz): 6 0,82 (d, 34,F, = 7,9 Hz, 2H, SiCH2), 0,99 (d, 3JH,H -= 6,9 Hz, 6H, CH(CH3)2), 1,24 (t, 34,H = 6,9 Hz, 9H, CH3CH20), 1,38 (d, 34,H = 6,9 Hz, 6H, CH(CH3)2), 2,23 (m, 2H, S1CH2CH2), 2,27 (s, 3H, plc-Me), 3,10 (h, 25 JH,H= 6,9 Hz, 6H, CH(CH3)2), 3,85 (c, 3JH H = 6,9 Hz, 6H, CH3CH20), 4,68 (t, 34,H -= 7,9 Hz, 2H, CH2Imz), 6,98 (2 x t, 3H, 34,H = 6,6 Hz, 34,H = 2,0 Hz, Imz-H4 y o-pic, solapados), 7,13 (d, 3JH,H = 2,0 Hz, 1H, Imz-H5), 7,28 ((1, 34,H = 7,9 Hz, 2H, m-Ph), 7,46 (t, 34,H = 7,9 Hz, 1H, p-Ph), 8,54 (d, 3JH,F, = 6,6 Hz, 2H, 0-plc). RMN 13C{1H} (CDCI3, 75 MHz): ô 7,7 (S1CH2), 18,4 (CH3CH20), 21,0 (plc-Me), 23,2 (S1CH2CH2), 23,9 (CH(CH3)2), 26,5 30 (CH(CH3)2), 28,8 (CH(CH3)2), 55,4 (CH2Irnz), 58,6 (CH3CH20), 120,3 y 130,3 (Imz-C4 y C5), 124,2 (m-Ph), 125,1 (m-plc), 126,7 (p-Ph), 134,7 (ipso-Ph), 147,0 (o-Ph), 149,1 (p-33
5 pie), 152,8 (o-pic). ). IR (KBr): v 3030-3133 (m, arC-H st), 1619 (m, arC=C st), 1503 (s, C=N st), 1400-1460 (m, arC=C st), 1077 (w, Si-O-C st), 957 (w, Si-O-C st), 804 (m, Si-C st), 692 cm-1 (m, Si-0 st). MS (ESI+/TOF, CH2C12/Me0H/NH4HCOO 5 mM): rn/z 904,0818 [M + Nftsr, 887,0560 [M + H]. /-=\ (Eto)3si N y N-ip r2 Ph I-pd-I Ejemplo 13. Prepared& del complejo de plata 3(Si)1. 10 En una ampolla de 50 mL se peso la sal de imidazolio 2(Si)1 descrita en el Ejemplo 4 (1,28 g, 3,5 mmol) y el oxido de plata (0,40 g, 1,7 mmol), y se hizo vacio durante 10 min. Se suspendi6 el sOlido en 10 mL de diciorometano bajo arg6n y se dejo agitando la nnezcla a temperatura ambiente durante 16 h en ausencia de luz. Tras filtrar para eliminar el exceso de Oxido de plata, se evaporO la disolucion amarilla resultante y el residuo se 15 lavO con hexano (2 x 15 mL), obteniendose el producto 3(Si)1 como un sOlido aceitoso de color amarillo (1,48 g, 95%), cuya estructura en disoluciOn se corresponde con una formulaciOn [Ag(NHC)2][AgBr2] que da lugar a los rotameros syn y anti (70:30) en equilibrio. Anal. Calc. para C26H52N406Si2Ag2Br2 (948,43): C, 32,93; H, 5,53; N, 5,91%; Encontrado: C, 32,93; H, 5,28; N, 5,93%. RMN 1H (CDCI3, 300 MHz): IsOmero anti: 6 0,56 20 (t, 341,H = 7,7 Hz, 4H, SiCH2), 1,19 (t, 3JH,H = 6,9 Hz, 18H, CH3CH20), 1,88 (m, 4H, SiCH2CH2), 3,76 (s, 6H, lmz-Me), 3,78 (c, 34,H = 6,9 Hz, 12H, CH3CH20), 4,08 (t, 34,H = 7,7 Hz, 4H, CH2Imz), 6,91 y 6,94 (d, 34,H = 1,5 Hz, 2H, Imz-H4y Fr). IsOmero syn: 6 0,55 (t, 34,11 = 7,7 Hz, 4H, SiCH2), 1,18 (t, 3,11-1,11 = 6,9 Hz, 18H, CH3CH20), 1,88 (m, 4H, SiCH2CH2), 3,78 (c, 3.401 = 6,9 Hz, 12H, CH3CH20), 3,79 (s, 6H, lmz-Me), 4,06 (t, 34,H = 25 7,7 Hz, 4H, CH2Imz), 6,93 y 6,98 (d, 3s/H,H = 1,5 Hz, 2H, Imz-H4y Fr). RMN "G{1H} (CDCI3, 75 MHz): IsOmero anti: 6 8,7 (SiCH2), 18,2 (CH3CH20), 25,6 (SiCH2CH2), 38,9 (lmz-Me), 54,1 (CH2Imz), 58,3 (CH3CH20), 121,2 y 122,1 (Imz-C4 y C5), 181,7 (Imz-C2). IsOnnero syn: 67,3 (S1CH2), 18,2 (CH3CH20), 25,2 (S1CH2CH2), 38,7 (lmz-Me), 53,9 (CH2Imz), 58,5 (CH3CH20), 121,0 y 122,0 (Imz-C4 y C5), 181,2 (Imz-C2). Coeficientes de difusion DOSY-30 NMR (CDCI3, 25 °C) en tomb a 6,0.10-10 M2S-1 para los dos rotameros. MS (ESI+/TOF, CH2C12/Me0H/NH4HCOO 5 mM): nilz 681,2542 [Ag(NHC)2], 287,1814 [NHC + H]. 34
AgBr 3(Si)1 Ejemplo 14. Preparacion del complejo de plata 3(51)2. 5 El compuesto 3(Si)2 se prepar6 de como se describe para el complejo 3(Si)1 del Ejemplo 13, partiendo de la sal de imidazolio 2(51)2 descrita en el Ejemplo 5 (2,69 g, 5,7 mmol) y Oxido de plata (0,66 g, 2,8 mmol). El complejo 3(Si)2 se obtuvo como un sOlido aceitoso de color amarillo (3,07 g, 98%), cuya estructura en disolucion se corresponde con una 10 fornnulaciOn [Ag(NHC)2][AgBr2] que da lugar a los rotameros syn y anti (70:30) en equilibrio. Anal. Calc. para C42H68N406Si2Ag2Br2-0,7CH2C12 (1207,69): C, 42,17; H, 5,75; N, 4,81%; Encontrado: C, 41,83; H, 5,16; N, 5,27%. RMN 1H (CDCI3, 300 MHz): IsOmeros anti y syn: (50,57 (m, 8H, SiCH2), 1,21 (t, 3.4th = 7,0 Hz, 36H, CH3CH20), 1,79 (m, 8H, SiCH2CH2), 1,93 (s, 24H, Mes-o-Me), 2,29 (s, 12H, Mes-p-Me), 3,79 (c, 34,H = 7,0 Hz, 15 24H, CH3CH20), 4,18 (m, 8H, CH2Imz), 6,89 y 7,18(2 x d, 3JR,H = 1,5 Hz,2 x 4H, Imz-H4 y H5), 6,91 (s, 8H, m-Mes). RMN 13C{1H} (CDCI3, 75 MHz): Isomero anti: (58,5 (SiCH2), 17,7 (CH3CH20), 21,0 (Mes-p-Me), 25,7 (SiCH2CH2), 29,1 (Mes-o-Me), 53,7 (CH2Imz), 58,1 (CH3CH20), 121,6y 123,9 (Imz-C4 y C5), 129,4 (m-Mes), 134,6 (o-Mes), 135,3 (ipso-Mes), 139,1 (p-Mes). Isomero syn: 6 7,3 (SiCH2), 18,3 (CH3CH20), 21,0 (Mes-p-Me), 25,3 20 (SiCH2CH2), 29,1 (Mes-o-Me), 54,0 (CH2Imz), 58,5 (CH3CH20), 120,9 y 122,5 (Imz-C4 y C5), 129,1 (m-Mes), 134,7 (o-Mes), 135,6 (ipso-Mes), 139,3 (p-Mes). Coeficientes de difusi6n DOSY-NMR (CDCI3, 25°C) en torno a 5,8.10.10 M2S-1 para los dos rotanneros. MS (ESI+/TOF, CH2C12/Me0H/NH4HCOO 5 mM): m/z 889,3779 [Ag(NFIC)2I. 25 1==N N'mes AgBr 3(Si)2 Ejemplo 15. Preparacion del complejo de plata 3(51)3. El compuesto 3(Si)3 se preparO de como se describe para el complejo 3(Si)1 del Ejemplo 30 13, partiendo de la sal de imidazolio 2(Si)3 descrita en el Ejennplo 6 (2,50 g, 5,2 mmol) y 35
6xido de plata (0,60 g, 2,6 mmol). El complejo 3(S1)3 se obtuvo como un solid° aceitoso de color amarillo (3,14 g, 98%), cuya estructura en disoluciOn se corresponde con una formulacion [Ag(NHC)2][AgBr2] que da lugar a los rotameros syn y anti (70:30) en equilibrio. Anal. Calc. para C48F180N406S12Ag2Br2 (1240,89): C, 46,46; H, 6,50; N, 4,51%; 5 Encontrado: C, 46,84; H, 6,88; N, 5,01%. RMN 1H (CDCI3, 300 MHz): IsOmeros anti y syn: (50,67 (m, 8H, S1CH2), 1,15 (d, 3,4th = 6,6 Hz, 24H, CH(CH3)2), 1,20 (d, 34,Ei = 6,6 Hz, 24H, CH(CH3)2), 1,21 (t, 34,H = 7,0 Hz, 36H, CH3CH20), 2,03 (m, 8H, SiCH2CH2), 2,36 (sep., 3JKH = 6,6 Hz, 8H, CH(CH3)2), 3,85 (c, 34,11 = 7,0 Hz, 24H, CH3CH20), 4,33 (m, 8H, CH2Imz), 7,00 y 7,20 (2 x d, 3.4tH = 1,7 Hz.2 x 4H, Imz-H4 y H5), 7,22 (d, 341,H = 7,7 Hz, 10 8H, m-Ph), 7,47 (t, 3JH,H = 7,7 Hz, 4H, p-Ph). RMN 13C{1H} (CDCI3, 75 MHz): IsOmero anti: (57,5 (SiCH2), 18,3 (CH3CH20), 24,3 (CH(CH3)2), 25,4 (SiCH2CH2), 28,1 (CH(CH3)2), 54,1 (CH2Imz), 58,6 (CH3CH20), 121,5 y 123,7 (Imz-C4 y C5), 124,2 (p-Ph), 129,7 (m-Ph), 145,6 (0-Ph), 145,9 (ipso-Ph). IsOmero syn: (5 7,3 (SiCH2), 18,3 (CH3CH20), 24,5 (CH(CH3)2), 25,2 (SiCH2CH2), 28,3 (CH(CH3)2), 53,7 (CH2Imz), 58,5 (CH3CH20), 121,5 y 15 123,7 (Imz-C4 y C5), 125,7 (p-Ph), 130,5 (m-Ph), 145,6 (0-Ph), 145,9 (ipso-Ph). Coeficientes de difusi6n DOSY-NMR (CDCI3, 25 °C) en tome a 5,7.10-10 M2S.1 para los dos rotameros. MS (ESI+/TOF, CH2C12/Me0H/NH4HCOO 5 mM): m/z 973,4667 [Ag(NHC)2]+. 20 /=\ AgBr 3(Si)3 Ejemplo 16. Preparacion del complejo de plata 3(A)1. El compuesto 3(A)1 se prepare) de forma similar a la descrita para el complejo 3(Si)1 del 25 Ejemplo 13, partiendo de la sal de imidazolio 2(A)1 descrita en el Ejemplo 7 (0,80 g, 3,7 mmol) y 6xido de plata (0,43 g, 1,9 mmol). El complejo 3(A)1 se obtuvo come un solido aceitoso de color amarillo (1,03 g, 88%). Anal. Calc. para C6FI11N3AgBr.0,1C6H14 (321,56): C, 24,65; H, 3,89; N, 13,07%; Encontrado: C, 24,95; H, 4,09; N, 13,25%. RMN 1H (CDCI3, 300 MHz): 63,09 (t, 34,H = 5,5 Hz, 2H, NH2CH2), 3,83 (s, 3H, Imz-Me), 4,14 (t, 34tH = 5,5 30 Hz, 2H, CH2Imz), 6,96 y 7,05 (2 x d,3JH,H = 1,8 Hz, 2 x 1H, Imz-H4 y H5). RMN 13C{1H} (CDCI3, 75 MHz): 638,8 (Imz-Me), 42,9 (NH2CH2), 54,7 (CH2Imz), 121,6 y 122,1 (Imz-C4 y C5), 180,8 (Imz-C2). MS (ESI+/TOF, CH2C1)/Me0H/NH4HCOO 5 mM): rniz 287,1763 [M - Br + 3H2O]. 36
/=\ H2N N y AgBr 3(A)1 Ejemplo 17. Preparacion del complejo de plata 3(A)2. 5 El compuesto 3(A)2 se preparo de forma similar a la descrita para el complejo 3(Si)1 del Ejemplo 13, partiendo de la sal de imidazolio 2(A)2 descrita en el Ejemplo 8 (3,20 g, 10,0 rnmol) y 6xido de plata (1,18 g, 5,1 mmol). El complejo 3(A)2 se obtuvo como un sOlido aceitoso de color amarillo (3,60 g, 86%). Anal. Calc. para C14H19N3AgBr.0,15(C6F114) 10 (430,02): C, 41,61; H, 4,95; N, 9,77%; Encontrado: C, 42,07; H, 4,91; N, 10,29%. RMN 1H (CDCI3, 300 MHz): 6 1,93 (s, 6H, Mes-o-Me), 2,31 (s, 3H, Mes-p-Me), 3,15 (t, 34H = 5,6 Hz, 2H, NH2CH2), 4,25 (1, 34,H = 5,6 Hz, 2H, CH2Imz), 6,91 y 7,28 (2 x d, 34,H = 1,7 Hz, 2 x 1H, Imz-H4 y H5), 6,92 (s, 2H, m-Mes). RMN 13C{1H} (CDCI3, 75 MHz): 6 17,7 (Mes-p-Me), 21,1 (Mes-o-Me), 43,1 (CH2Imz), 55,0 (NH2CH2), 121,4 y 122,6 (Imz-C4 y C5), 129,4 15 (m-Mes), 135,3 (ipso-Mes), 134,6 (o-Mes), 139,6 (p-Mes), 180,2 (Imz-C2). MS (ES1+/TOF CH2C12/Me0H/NH4HCOO 5 mM): m/z 230.1656 [M - AgBr + H]. H2N"----1yN-Mes AgBr 3(A)2 20 Ejemplo 18. Preparacion del complejo de plata 3(A)3. El compuesto 3(A)3 se prepar6 de forma similar a la descrita para el complejo 3(Si)1 del Ejemplo 13, partiendo de la sal de imidazolio 2(A)3 descrita en el Ejemplo 9 (3,60 g, 10,3 mmol) y 6xido de plata (1,18 g, 5,1 mmol). El complejo 3(A)3 se obtuvo como un solido 25 aceitoso de color amarillo (4,30 g, 90%). Anal. Calc. para C17H25N3AgBr.0,25(C6I-I14) (480,72): C, 46,22; H, 5,98; N, 8,74%; Encontrado: C, 46,75; H, 5,72; N, 8,53%. RMN1H (CDCI3, 300 MHz): 61,11 (d, 3,41,H = 6,9 Hz, 12H, CH(CH3)2), 1,18 (d, JH,H = 6,9 Hz, 12H, CH(CH3)2), 2,32 (sep., 3.4th = 6,9 Hz, 2H, (C1-13)2CH), 3,17 (t, 34,H = 5,8 Hz, 2H, NH2CH2), 4,26 (t, 3JKH = 5,8 Hz, 2H, CH2Imz), 6,98 y 7,31 (2 x d, 3JH,H = 1,5 Hz, 2 x 1H, Imz-H4 y 30 H5), 7,23 (d, 3.4tH = 7,7 Hz, 2H, m-Ph), 7,45 (t, 34,H = 7,7 Hz, 1H, p-Ph). RMN 13C{1H} 37
5 (CDCI3, 75 MHz): 6 24,3 (CH(CH3)2), 24,6 (CH(CH3)2), 28,3 (CH(CH3)2), 43,2 (NH2CH2), 55,0 (CH2Imz), 121,2 y 123,9 (Irriz-C4 y C5), 124,3 (m-Ph), 130,5 (ipso-Ph), 134,6 (o-Ph), 145,6 (p-Ph), 182,8 (Imz-C2). MS (ESI+/TOF, CH2C12/Me0H/NH4HCOO 5 mM): m/z 272,2139 [M - AgBr + H]. Fi2NNy N'iPr2Ph AgBr 3(A)3 Ejemplo 19. Preparacion del complejo de paladio 11(S1)1. 10 En una ampolla de 50 mL se pesaron el carbeno de plata 3(Si)1 descrito en el Ejemplo 13 (0,39 g, 0,87 mmol) y PdBr2(COD) (0,16 g, 0,43 mmol; COD = 1,5-ciclooctadieno). Despues de someter los solidos a vacio durante 5 min, se disolviO el sOlido bajo arg6n en 10 mL de diclorometano y la disoluciOn naranja resultante se dej6 agitando a temperatura ambiente durante 1 h. Se filtrO la mezcla para separar el haluro de plata que se forma 15 coma producto secundario, se evapor6 Is disoluciOn amarilla resultante y se lavO con hexano (2 x 15 mL), obteniendose el product° II(Si)1 como un sOlido pulverulento de color arnarillo (0,65 g, 89%), cuya estructura en disoluciOn se corresponde con la presencia de los rotameros trans-syn y trans-anti (50:50) en equilibria. Anal. Calc. para C26H52N406Si2PdBr2 (839,11): C, 37,22; H 3,25; N 6,68%; Encontrado: C, 36,97; H, 6,07; 20 N, 6,79%. RMN 1H (CDCI3, 300 MHz): IsOrnero anti: 6 0,72 (m, 4H, SiCH2), 1,20 (t, 3J1-1,H = 6,9 Hz, 18H, CH3CH20), 2,20 (m, 4H, SiCH2CH2), 3,81 (c, 3JH,H = 6,9 Hz, 12H, CH3CH20), 4,06 (s, 6H, Imz-Me), 4,44 (m, 4H, CH2Imz), 6,79 y 6,88 (2 x d, 3.1H,H = 1,7 Hz, 2 x 2H, Imz-H4 y H5). IsOmero syn: 60,72 (m, 4H, SiCH2), 1,20 (t, 3../H,H= 6,9 Hz, 18H, CH3CH20), 2,20 (m, 4H, SiCH2CH2), 3,81 (c, 34tH = 6,9 Hz, 12H, CH3CH20), 4,03 (s, 6H, lmz-Me), 25 4,44 (m, 4H, CH2Imz), 6,79 y 6,86 (2 x d, 34.1,H = 1,7 Hz, 2 x 2H, Imz-H4 y H5). RMN 13C(1H) (CDCI3, 75 MHz): Isomer° anti: 6 7,7 (SiCH2), 18,3 (CH3CH20), 24,4 (SiCH2CF12), 37,9 (lmz-Me), 53,1 (CH2Imz), 58,6 (CH3CFI20), 121,1 y 121,8 (Imz-C4 y C5), 169,2 (Imz-C4). IsOmero syn: 6 7,5 (SiCH2), 18,3 (CH3CH20), 24,3 (SiCH2CH2), 37,9 (Imz-Me), 52,8 (CH2Imz), 58,5 (CH3CH20), 121,0 y 121,7 (Imz-C4 y C5), 169,2 (Imz-C2). IR (KBr): v 3080- 30 3150 (m, arC-H st), 1525 (s, C=N st), 1380-1480 (m, arC=C st), 1080 (w, Si-O-C st), 960 (w, Si-O-C st), 720-790 (m, Si-C st), 690 cm-1 (m, Si-0 st). MS (ESI+/TOF, CH2C12/Me0H/NH4HCOO 5 mM): m/z 856,1157 [M + NH41+, 759,1635 [M - Br]. 38
Br-Pd-Br ,INNSi(OEt)3 \==.1 II(Si)1 Ejemplo 20. Preparacion del complejo de paladio 11(S1)2. 5 El compuesto II(Si)2 se prepar6 del mismo modo que el compuesto II(Si)1 del Ejemplo 19, partiendo del carbeno de plata 3(Si)2 descrito en el Ejemplo 14 (0,45 g, 0,81 mmol) y de PdBr2(COD) (0,15 g, 0,41 mmol). El complejo 11(S1)2 se obtuvo como un sOlido pulverulento de color amarillo (0,83 g 97%), cuya estructura en disolucion se corresponde con la presencia de los rotameros trans-syn y trans-anti (56:44) en equilibrio. 10 Anal. Cale. C42F168N406Si2PdBr2 (1047,41): C, 48,16; H, 6,54; N, 5,35%; Encontrado: C, 48,41; H, 6,44; N, 5,41%. RMN 1H (CDCI3, 300 MHz): IsOmero anti: ô0,47 (m, 4H, SiCH2), 1,20 (m, 18H, CH3CH20), 1,89 (m, 4H, SiCH2CH2), 2,22 (s, 12H, Mes-o-Me), 2,33 (s, 6H, Mes-p-Me), 3,83 (m, 12H, CH3CH20), 4,17 (m, 4H, CH2Imz), 6,70 y 6,98 (2 x d, 34,H = 1,5 Hz, 2 x 2H, Imz-H4 y H5), 6,94 (s, 4H, m-Mes). Isomero syn: 6 0,73 (m, 4H, SiCH2), 1,23 15 (m, 18H, CH3CH20), 1,89 (m, 4H, SiCH2CH2), 1,91 (s, 12H, Mes-o-Me), 2,43 (s, 6H, Mes-p-Me), 3,81 (m, 12H, CH3CH20), 4,61 (m, 4H, CH2Imz), 6,63 y 6,93 (2 x d, 34,H = 1,5 Hz, 2 x 2H, Imz-H4 y H5), 6,81 (s, 4H, m-Mes). RMN 13C{1H} (CDCI3, 75 MHz): IsOmero anti: 6 7,1 (SiCH2), 18,4 (CH3CH20), 19,4 (Mes-p-Me), 23,9 (SiCH2CH2), 29,7 (Mes-o-Me), 53,1 (CH2Imz), 58,4 (CH3CH20), 120,8 y 122,7 (Imz-C4 y C5), 128,8 (m-Mes), 136,0 (ipso-20 Mes), 136,6 (o-Mes), 138,2 (p-Me), 169,7 (Imz-C2). Isonnero syn: 6 7,5 (SiCH2), 19,8 (CH3CH20), 21,0 (Mes-p-Me), 24,3 (S1CH2CH2), 29,3 (Mes-o-Me), 53,7 (CH2Imz), 58,4 (CH3CH20), 121,1 y 122,7 (Imz-C4 y C5), 128,7 (m-Mes), 135,5 (ipso-Mes), 135,9 (o-Mes), 137,4 (p-Mes), 169,6 (Imz-C2). IR (KBr): v 3080-3170 (m, arC-H st), 1620 (m, arC=C st), 1590 (s, C=N st), 1380-1450 (m, arC=C st), 1072 (w, Si-O-C st), 943 (w, Si-O-C st), 722- 25 800 (m, Si-C st), 703 cm-1 (m, Si-0 st). MS (ESI+/TOF, CH2C12/Me0H/NH4FICOO 5 mM): m/z 1064,2414 [M + NH4]. 39
f=\ N N si(OEt)3 II(Si)2 Ejemplo 21. Preparacion del complejo de paladioll(S1)3. 5 El compuesto II(Si)3 se prepar6 como se ha descrito para el compuesto II(Si)1 del Ejemplo 19, partiendo del carbeno de plata 3(Si)3 descrito en el Ejemplo 15 (0,44 g, 0,70 mmol) y de PdBr2(COD) (0,13 g, 0,35 mmol). El complejo II(Si)3 se obtuvo como un solid° pulverulento de color amarillo (0,75 g, 95%), cuya estructura en disolucion se corresponde con la presencia de los rotameros trans-syn y trans-anti (60:40) en equilibrio. 10 Anal. Calc. C48F180N406S12PdBr2 (1131,57): C, 50,95; H, 7,13; N, 4,95%; Encontrado: C, 50,86; H 6,63; N 5,07%. RMN 1H (DMSO-d6, 300 MHz): IsOmero anti: ó 0,49 (m, 4H, SiCH2), 1,13 (m, 42H, CH(CH3)2, CH3CH20), 1,89 (m, 4H, S1CH2CH2), 2,45 (m, 4H, CH(CH3)2), 3,72 (m, 12H, CH3CH20), 4,07 (m, 4H, CH2Imz), 7,15-7,80 (m, 10H, y H5, p-Ph, m-Ph). IsOmero syn: 6 0,58 (m, 4H, SiCH2), 1,13 (m, 42H, CH(CH3)2, CH3CH20), 15 1,89 (m, 4H, SiCH2CH2), 2,45 (m, 4H, CH(CH3)2), 3,72 (m, 12H, CH3CH20), 4,20 (m, 4H, CH2Imz), 7,15-7,80 (m, 10H, y H5, p-Ph, m-Ph). RMN 13C(1H) (DMSO-d6, 75 MHz): 6 8,7 (SiCH2), 14,6 (CH3CH20), 23,1 (SiCH2CH2), 23,6 (CH(C1-13)2), 27,3 (CH(CH3)2), 52,6 (CH2Imz), 57,4 (CH3CH20), 121,1 y 122,2 (Imz-C4 y C5), 123,4 (p-Ph), 129,6 (m-Ph), 134,1 (ipso-Ph), 144,4 (o-Ph). IR (KBr): v 3030-3120 (m, arC-H st), 1625 (m, arC=C st), 20 1512 (s, C=N st), 1330-1500 (m, arC=C st), 1123 (w, Si-O-C st), 946 (w, Si-O-C st), 700- 800 (m, Si-C st), 685 cm-1 (m, Si-0 st). MS (ESI+/TOF, CH2C12/Me0H/NH4HCOO 5 mM): mtz 899,3888 [M - 4Et0H - Br + Me0H], 856,1127 [M - 5Et0H - Br + NH401-11+, 776,1865 [M - 6Et0H - Brr. 25 \ (Et0)3S1NyN'1Pr2Ph Br--Pd-Br PhiPr2-1,(INNi(OEt) II(Si)3 Ejemplo 22. Preparacion del complejo de paladio II(A)1. 40
El compuesto II(A)1 se prepare) como se ha descrito para el connpuesto II(Si)1 del Ejemplo 19, partiendo del carbeno de plata 3(A)1 descrito en el Ejemplo 16 (1,00 g, 3,2 mmol) y de PdBr2(COD) (0,60 g, 1,6 mmol). El complejo II(A)1 se obtuvo como un solid° 5 amarillo aceitoso (0,70 g, 85%), cuya carac:terizaciOn por RMN requirio su transformaci6n en la sal de amonio, [II(A)1]2+, par tratamiento con un exceso de NH4CI y cuya estructura en disoluciOn se corresponde con la presencia de los rotameros trans-syn y trans-anti (30:70) en equilibria. Anal. Cale. C12H22N6PdBr2 (516,57): C, 27,90; H, 4,29; N, 16,27%; Encontrado: C, 28,10; H 4,76; N, 16,05 %. RMN 1H (DMSO-d6, 300 MHz, [II(A)1]2+): 10 Isomero anti: 6 2,88 (t, 34th = 5,6 Hz, 4H, CH2Imz), 3,83 (s, 6H, Imz-Me), 4,08 (t, 3JH,H=" 5,6 Hz, 4H, NH2CH2), 7,67 y 7,70 (2 x s, 2 x 2H, Imz-H4 y H5). Isomer° syn: 6 2,88 (t, = 5,6 Hz, 4H, CH2Imz), 3,74 (s, 6H, Imz-Me), 4,24 (t, 34,H = 5,6 Hz, 4H, NH2CH2), 7,40 y 7,43 (2 x s, 2 x 2H, Imz-H4 y H5). RMN 13C{1H} (DMSO-d6, 75 MHz, [II(A)1]2+): IsOmero anti: 6 37,6 (Imz-Me), 40,8 (CH2Imz), 51,5 (NH2CH2), 122,0 y 122,8 (Imz-C4 y 15 C6), 177,8 (Imz-C2). gHMBC-{1H, 16N} (CDCI3, 293K): 6 -190 (Num), -198 (km), -345 (NH2). MS (ES1÷/TOF, CH2C12/Me0H/NH4HCOO 5 mM): al& 453,1629 [M - HBr NH4l÷, 436,1562 [M - Br], 355,0865 [M -HBr - Br]. 20 ir=\ H2 NyN 1\1-' Br-Pd-Br II(A)1 Ejemplo 23. Preparacion del complejo de paladio II(A)2. El compuesto II(A)2 se preparO coma se ha descrito para el compuesto II(Si)1 del Ejemplo 19, partiendo del carbeno de plate 3(A)2 descrito en el Ejemplo 17 (0,50 g, 1,2 25 mmol) y de PdBr2(COD) (0,22 g, 0,60 mmol). El cornplejo II(A)2 se obtuvo coma un sOlido amarillo aceitoso (0,38 g, 88%), cuya caracterizaciOn par RMN requiriO su transformaci6n en la sal de amonio, [II(A)212, par tratamiento con un exceso de NH4Cly cuya estructura en disolucion se corresponde con la presencia de los rotameros trans-syn y trans-anti (20:80) en equilibria. Anal. Cale. C28H38N6PdBr2 (724,87): C, 46,39; H, 5,28; N, 11,59%; 30 Encontrado: C, 46,44; H, 5,78; N, 11,59%. RMN 1H (DMSO-d6, 300 MHz, [II(A)2]2+): Isomer° anti: 6 1,85 (s, 12H, Mes-o-Me), 2,32 (s, 6H, Mes-p-Me), 2,93 (t, 34,H = 5,8 Hz, 41
4H, CH2Imz), 4,12 (t, 341,11 = 5,8 Hz, 4H, NH2CH2), 7,02 (s, 4H, m-Mes), 7,44 y 7,67 (2 x d, 3.41,H = 1,8 Hz, 2 x 2H, Imz-H4y H5). IsOmero syn: (51,91 (s, 12H, Mes-o-Me), 2,36 (s, 6H, Mes-p-Me), 2,96 (t, 3.41,H = 5,8 Hz, 4H, CH2Imz), 4,19 (t, 3JitH = 5,8 Hz, 4H, NH2CH2), 6,92 (s, 4H, m-Mes), 7,36 y 7,62 (2 x d, 3JH,H = 1,7 Hz, 2 x 2H, Imz-H4y H5). RMN 13C{1H} 5 (DMSO-d6, 75 MHz, [II(A)2]2+): IsOmero anti: (516,7 (Mes-p-Me), 20,1 (Mes-o-Me), 43,4 (CH2Imz), 53,6 (NH2CH2), 121,9 y 122,5 (Imz-C4y C5), 128,4 (m-Mes), 128,7 (ipso-Mes), 134,0 (o-Mes), 137,9 (p-Mes), 171,5 (Imz-C2). gHMBC-{1H, 15N} (CDCI3, 293K): (5-191 (Nimz), -192 (Nirriz), -368 (NH2). MS (ESI+/TOF, CH2C12/Me0H/NH4HCOO 5 mM): m/z 644,9697 [M - Br], 563,2124 [M - Br - HBr]+. 10 /=\ NyN.mes H2N Br-Pd-Br Mes -NH2 N N - \_=/ II(A)2 Ejemplo 24. Preparaciem del complejo de paladio II(A)3. 15 El compuesto II(A)3 se preparO como se ha descrito para el compuesto II(Si)1 del Ejemplo 19, partiendo del carbeno de plata 3(A)3 descrito en el Ejennplo 18 (0,50 g, 0,85 nnmol) y de PdBr2(COD) (0,16 g, 0,42 mmol). El complejo II(A)3 se obtuvo como un sOlido amarillo aceitoso (0,58 g, 84%), cuya caracterizacion por RMN requirio su transformacion en la sal de amonio, [II(A)3]2+, por tratamiento con un exceso de NRICI y cuya estructura 20 en disolucion se corresponde con la presencia de los rotameros trans-syn y trans-anti (25:75) en equilibrio. Anal. Calc. C34HSON6PdBr2 (809,03): C, 50,48; H, 6,23; N, 10,39%; Encontrado: C, 50,07; H, 5,98; N, 10,13%. 1H NMR (DMSO-d6, 300 MHz, [II(A)3]2+): IsOmero anti: 61,07 (d, 3,4tH = 6,9 Hz, 24H, CH(CH3)2), 2,26 (sep., 3JKH = 6,9 Hz, 4H, CH(CH3)2), 2,89 (m, 4H, CH2Imz), 4,08 (m, 4H, NH2CH2), 7,32 (d, 3JKH = 7,9 Hz, 4H, m-25 Ph), 7,49 (t, 3JH,H = 7,9 Hz, 2H, p-Ph), 7,61 y 7,71 (2 x d, 3JH,H = 1,6 Hz, 2 x 2H, Innz-H4 y H5). IsOmero syn: 61,12 (d, 34H = 6,9 Hz, 24H, CH(CH3)2), 2,26 (sep., 3JH,H = 6,9 Hz, 4H, CH(CH3)2), 2,99 (m, 4H, CH2Imz), 4,22 (m, 4H, NH2CH2), 7,32 (d, 3.404= 7,7 Hz, 4H, m-Ph), 7,45 (t, 3JH,H = 7,7 Hz, 2H, p-Ph), 7,59 y 7,67 (2 x d, 34H = 1,5 Hz, 2 x 2H, Imz-H4 y H5). 13C{1H} NMR (DMSO-d6, 75 MHz, [II(A)3]2+): IsOmero anti: 23,3 (CH(CH3)2), 23,6 30 CH(CH3)2), 27,2 (CH(CH3)2), 42,5 (CH2Innz), 53,5 (NH2CH2), 121,9 y 123,9 (Imz-C4 y C5), 123,4 (m-Ph), 129,5 (ipso-Ph), 134,5 (o-Ph), 144,9 (p-Ph), 181,3 (Imz-C2). gHMBC-{1H, 42
5 15N} (CDCI3, 293K): 6 -187 (Nim,), --205 (Nmz), -377 (NH2). MS (ESI+/TOF, CH2C12/Me0H/NR4HCOO 5 mM): m/z 837,3255 [M - Br + HCOOH + HCOONH4r, 755,4001 [M - 2HBr + 2HCOOH + NH4]. H2N'.--NyN'1Pr2Ph Br-Pd-Br II(A)3 Ejemplo 25. Preparacion de la sal de imidazolio 4.4. En una ampolla de 25 mL se coloco el bis(imidazolil)metano de partida (0,26 g, 1,7 mmol) 10 y la N-(2-bromoetil)ftalimida (1,11 g, 4,4 mmol). Despues de someter los solidos a vacio durante 5 min, se disolvieron en 5 mL de CH3CN seco y se calentO la disoluciOn resultante a 120 °C durante 48 h. Tras filtrar y secar el solid°, se obtuvo la sal 4.4 como un solid° pulverulento de color blanco (1,05 g, 91%). Anal. Calc. para C27F124N604Br2.2H20 (692,36): C, 46,84; H, 4,08; N, 12,14%; Encontrado: C, 47,03; H, 15 4,01; N, 12,03%. RMN 1H (DMSO-d6, 300 MHz): 6 3,99 (t, 34,H = 4,6 Hz, 4H, CH2ftal), 4,53 (t, 3,44,H = 4,6 Hz, 4H, CH2Imz), 6,71 (s, 2H, CH2), 7,82 (s, 8H, o-ftal, m-ftal), 7,92 y 8,02 (2 x s, 2 x 2H, Imz-H4 y H5), 9,56 (s, 2H, Imz-H2). RMN 13C{1H} (DMSO-d6, 75 MHz): 6 37,4 (CH2ftal), 47,9 (CH2Imz), 57,8 (CH2), 121,5 y 123,4 (Imz-C4 y C5), 122,7 (o-ftal), 131,0 (ipso-ftal), 134,1 (m-ftal), 137,6 (Imz-C2), 167,2 (C=0). MS (ESI+/TOF, 20 CH2C12/Me0H/NH4HCOO 5 nnM): m/z 495,1763 [M - HBr - Br]. 25 N1 1,1:1\1 r) Br- Br 4.4 Ejemplo 26. Preparacion del connplejo quelato de paladio 5.4. 43
En una ampolla de 15 mL con tapa roscada se peso la sal de bisimidazolio 4.4 descrita en el Ejemplo 25 (0,50 g, 0,76 mnnol) y se disolvi6 en 1 mL de DMSO, sobre esa disolucion se anadi6 un equivalente de acetato de paladio (0,17 g, 0,76 mmol). La suspensiOn resultante se calentO a 50 °C con agitaciOn durante 2 h. Tras estas 2 h, se 5 subi6 progresivamente la temperatura hasta 110 °C a lo largo de 3 h. La disolucion rojiza resultante se pas() a traves de una columna de celite de unos 2,0 cm de altura y 1,5 cm de diametro. Tras evaporar el DMSO y secar el sOlido, se obtuvo el carbeno quelato de paladio 5.4 conno un solid° de color gris (0,49 g, 85%). Anal. Calc. para C27H22N604PdBr2.H20 (778,74): C, 41,64; H, 3,11; N, 10,79%; Encontrado: C, 41,48; H, 10 3,23; N, 10,95%. RMN 1H (DMSO-d6, 300 MHz): 3,80-4,10 (2 x m, 2 x 2H, CH2ftal), 4,11 y 5,15 (2 x m, 2 x 2H, CH2Imz), 6,25 (m, 2H, CH2), 7,33 y 7,52 (2 x s, 2 x 1H, Imz-H4 y H5), 7,60 (s, 8H, o-ftal y m-ftal). RMN 13C{1H} (DMSO-d6, 75 MHz): 6 37,5 (CH2ftal), 48,5 (CH2Imz), 62,1 (CH2), 120,8 y 121,3 (Imz-C4 y C5), 122,3 (o-ftal), 130,7 (ipso-ftal), 133,6 (m-ftal), 159,6 (Imz-C2), 166,7 (C=0). MS (ESI+/TOF, CH2C12/MeOHNH4HCOO 5 mM): 15 m/z 761,039 [M + H], 697,126 [M - HBr+ NH4]+, 617,086 [M - 2HBr + )-N Br L-1 0 0 5.4 Ejemplo 27. Preparacion del complejo quelato de paladio III(A)4. 20 En una ampolla de 25 mL se peso el complejo de paladio 5.4 descrito en el Ejemplo 26 (1,00 g, 1,3 mmol) y se disolviO en 2 mL de CH3CN seco. Sobre la suspension formada, se anadieron 40 equivalentes de hidrazina (2,50 mL, 52,0 mmol), dando una disolucion transparente. Tras una hora de reacci6n a temperatura ambiente, se filtro la ftalilhidracina 25 formada, se evaporO el disolvente y se lave) con THF caliente utilizando un equipo soxhlet, obteniendose el producto III(A)4 curio un solid° beis (0,50 g, 82%). Anal. Cal. para C11H201\160PdBr2.H20 (518,54): C, 2548; H, 3,89; N, 16,21%; Encontrado C, 25,46; H, 4,02; N, 16,23%. RMN 1H (DMSO-d6, 300 MHz): 53,03 (s ancho, 4H, CH2Imz), 4,23 (s ancho, 4H, NH2CH2), 4,70 (s ancho, 4H, NH2), 6,34 (s, 2H, CH2), 7,62 y 7,69 (2 x s , 2 x 30 1H, Imz-H4 y Fr). RMN 13C{1H} (DMSO-d6, 75 MHz): 6 40,3 (CH2Imz), 49,3 (NH2CF12), 44
61,3 (CH2), 120,6 y 122,7 (Imz-C4 y C5), 152,0 (Imz-C2). gHMBC-{1H, 15N} (DMSO-d6, 293K): 5197 (Nim,), —203 (Nim,), —381 (NH2). IR (KBr): v 3393 (NH2 st), 3030-3100 (m, arC-H st), 1590-1610 (m, arC=C st), 1530 (s, C=N st), 1395-1480 cm-1 (m, arC=C st). MS (ESI+/TOF, CH2C12/Me0H/NH4HCOO 5 mM): miz 420,9814 [M — Br], 365,1714 [M — 2HBr 5 + Na], 339,0556 [M — HBr— Br]. eN )—N Pd r Br/ 'Br -1 H2N NH2 Ejemplo 28. Preparaci6n de PMC(S1)11. 10 III(A)4 En un vial Eppendorf de 25 mL se aniadieron 15 mg de PMs recubiertas de silice (Silica-Adembeads 300 nm de Ademtech: nude° de maghemita (y-Fe203); contenido en oxido metalico >70%, magnetizaciOn de saturaciOn: 40 emu/g; densidad de grano: 1,8-2 g/cm3; superficie especifica 10 m2/g), 1 mL de Tx (Tx = disoluciOn acuosa de TritonTm X405 at 15 0,21%v), 1 mL de etanol y 175 pL de una disoluciOn acuosa de amoniaco al 30%, para despues sonicar la muestra utilizando un instrumento Hielscher modelo UPS200S de 200 W, durante 5 min y a la mitad de su potencia maxima. En otro vial se pes6 el complejo l(Si)1 descrito en el Ejemplo 10 (93,75 pmol) y se disolviO en 4,5 mL de etanol. Bajo agitaciOn mecanica (utilizando un agitador/calefactor Bioshake iQ de Qlnstruments) sobre 20 la suspensiOn de PMs se adiciono gota a gota la disolucion del complejo durante 2,5 h, a 25 °C y 750 rpm y sonicando cada 15 min para favorecer la dispersion de las particulas. A continuacion se calento hasta 40 °C y se dej6 agitando 1 h mas a 750 rpm. Con ayuda de un iman externo, se decanto la disolucOn y se lavaron las particulas con etanol, con fracciones de 5 mL hasta que los lavados fueron incoloros, posteriormente se lavo con 25 Pluronic0 F127 (0,30 %v) (3 x 5 mL) y finalnnente con Tx (3 x 5 mL). Se obtuvieron las PMC(S1)11 como un sOlido pulverulento de color marr6n, que se conserv6 a 5 °C dispersado en 5 mL de Tx 0,21%. ICP-MS: 0,28 %w Pd. IR ATR: v 1620 (m, arC=C st), 1502 (s, C=N st), 1380-1480 (m, arC=C st), 800 cm-1 (m, Si-C st). TEM: particulas magneticas esforicas de tamafio comprendido entre 280-340 nm con un grosor promedio 30 del recubrimiento de silice de 1,5 nm para la capa de silice. 45
PMC(Si)11 Ejemplo 29. Preparacion de PMC(SI)12. -N 5 Las PMC(Si)I2 se prepararon como se ha descrito para PMC(Si)11 en el Ejemplo 28, pero utilizando el complejo l(S1)2 descrito en el Ejemplo 11. Se obtuvieron como un sOlido pulverulento de color marrOn, que se conserve) a 5°C dispersadas en 5 mL de Tx 0,21%. ICP-MS: 0,77 %w Pd. IR ATR: v 1615 (m, arC=C st), 1501 (s, C=N st), 1380-1480 (m, arC=C st), 780 cm-1 (m, Si-C st). TEM: particulas magneticas esfericas de tamatio 10 comprendido entre 265-345 nm con un grosor promedio del recubrimiento de silice de 2,0 nm para la capa de silice. PMC(Si)12 15 Ejemplo 30. Preparacion de PMC(SI)13. Las PMC(S1)13 se prepararon como se ha descrito para PMC(Si)11 en el Ejennplo 28, pero utilizando el complejo l(Si)3 descrito en el Ejemplo 12. Se obtuvieron como un solid° pulverulento de color marrem, que se conservo a 5 °C dispersadas en 5 mL de Tx 0,21%. 20 ICP-MS: 0,66 %w Pd. IR ATR: v 1560-1640 (m, arC=C st), 1330-1480 (m, arC=C st), 770 cm- (m, Si-C st). TEM: particulas magnOticas esfericas de tamatio comprendido entre 280-350 nm. 46
—0, HO;Si N N,. —0 y Pr2Ph 1—Pd—I PMC(Si)13 Ejemplo 31. Preparacion de PMC(S1)111. 5 Las PMC(Si)111 se prepararon como se ha descrito para PMC(Si)11 en el Ejemplo 28, pero utilizando el complejo II(Si)1 descrito en el Ejemplo 19. Se obtuvieron conno un sOlido pulverulento de color marr6n, que se conserve) a 5 °C dispersadas en 5 mL de Tx 0,21%. ICP-MS: 0,24 %w Pd. IR ATR: v3080-3150 (m, arC-H st), 1380-1530 (m, C=N st, arC=C st). TEM: particulas magneticas esfericas de tamailo comprendido entre 260-330 10 nm. LOSI 0 —0' y Br—Pd-Br —0,-Si 1-0 ‘=_/ PMC(S1)111 Ejemplo 32. Preparacion de PMC(S1)112. 15 Las PMC(S1)112 se prepararon corn° se ha descrito para PMC(S1)11 en el Ejemplo 28, pero utilizando el complejo II(S1)2 descrito en el Ejemplo 20. Se obtuvieron como un solid° pulverulento de color marron, que se conserv6 a 5 °C dispersadas en 5 mL de Tx 0,21%. ICP-MS: 0,51 %w Pd. IR ATR: v 3060-3200 (m, arC-H st), 1620-1650 (s, arC=C 20 st), 1350-1520 (m, C=N st, arC=C st). TEM: particulas magneticas esfericas de tamatio comprendido entre 290-350 nm. 47
a) /—=\ C:I;Si ,NyN,mes —0 0 .0 Br—Pd-Br = in F°C)3Si -'----.'N N' PMC(Si)112 Ejemplo 33. Preparacion de PMC(S1)113. Mes —N 5 Las PMC(S1)113 se prepararon como se ha descrito para PMC(Si)11 en el Ejemplo 28, pero utilizando el complejo II(51)3 descrito en el Ejemplo 21. Se obtuvieron como un sOlido pulverulento de color marron, que se conservO a 5 °C dispersadas en 5 mL de Tx 0,21%. ICP-MS: 0,43 %w Pd. IR ATR: v 3050-3180 (m, arC-H st), 1620-1650 (s, arC=C st), 1380-1520 (m, C=N st, arC=C st). TEM: particulas magneticas esfericas de tamario 10 comprendido entre 280-360 nm. 0, /=\ N.. 0' y 'Pr2Ph Br—Pd-Br 0, iPr2Ph 1:2( PMC(Si)113 Ejemplo 34. Prepared& de PMC(A)I11. 15 En un vial de 5 mL se pesaron 15 mg de de PMs recubiertas de poliestireno entrecruzado funcionalizado con grupos acido carboxilico (Carboxyl-Adembeads 200 nm de Ademtech: nude° de maghemita (y-Fe203); contenido en Oxido metalico >70%, nnagnetizaciOn de saturacion: 40 emu/g; 300 mmol COOH/g de MNPs, densidad de grupos COOH en 20 superficie: 20 pmol/m2, densidad de grano: 1,8-2 g/cm3; superficie especifica 15 m2/g) que se suspendieron en 1,5 mL de Tx/Me0H (2:1; Tx = disoluciOn acuosa de TritOnTm X405 al 0,21%v) y se sonicaron con un instrumento Hielscher modelo UPS200S de 200 W durante 5 min y a la mitad de su potencia maxima. Por otro lado se preparO una disolucion en DMF del complejo 11(A)1 descrito en el Ejemplo 22 (45 pmol). Se colocaron 25 250 pL de ambas mezclas en seis viales Eppendorf de 1,5 mL utilizados, de tal forma que 48
cada uno de ellos contenia 0,75 pmol de grupos COOH y 15,0 pmol de grupos NH, y sobre cada uno se ariadieron 200 pL de una disoluciOn de carbodiimida CHMC (N-ciclohexil-N'-(24N-metilmorfolinoletil)carbodiimida) en Tx ([CHMC] = 0,03 my Se completO cada vial Eppendorf con 350 pL de Tx/Me0H (2:1) hasta un volumen final de 1 mL en 5 cada vial. Una vez preparadas las seis muestras, se pusieron bajo agitaciOn mecanica (utilizando un agitador de carrusel "rotator SB2" de Stuart) a 20 rpm durante 16 h a temperature ambiente. Despues se decantaron las disoluciones con ayuda de un iman, se lavaron las Table 3 muestras sucesivamente con una disolucion acuosa de NaOH 10 mm (2 x 1 mL), con Tx (2 x 1 mL), con una mezcla THF/Tx (2:1) en fracciones de 1 mL 10 hasta que las aguas de lavado fueron incoloras. Se obtuvieron las PMC(A)II1 como un solido pulverulento de color marron, que se conservo a 5 °C dispersado en 1 mL de Tx 0,21%. ICP-MS: 0,26 %w Pd. IR (KBr): v2900-3000 (m, arC-H st), 1723 (C=0 st), 1601 (m, arC=C st), 1493 (s, C=N st), 1450-1480 (m, arC=C st), 1260 cm-1 (C-N St (amida)). pH en el punto isoelectrico del potencial Z: P.I. = 4,8 [P.I.(PMs de partida) = 2,9]. TEM: 15 particulas magneticas esfericas de tamano comprendido entre 160-230 nm. N— H y El N" Br—Pd-Br k=1 /IN PMC(A)111 Ejemplo 35. Preparaci6n de PMC(A)I12. 20 Las PMC(A)II2 se prepararon como se ha descrito para PMC(A)II1 en el Ejemplo 34, pero utilizando el complejo II(A)2 descrito en el Ejemplo 23. Se obtuvieron como un sOlido pulverulento de color marrOn, que se conservO a 5 °C dispersadas en 1 mL de Tx 0,21%. ICP-MS: 0,54 %w Pd. IR (KBr): v 2900-3000 (m, arC-H st), 1724 (C=0 st), 1601 (m, 25 arC=C st), 1492 (s, C=N st), 1450-1480 (m, rC=C st), 1260 cm-1 (C-N St (amida)). pH en el punto isoelectrico del potencial Z: P.1. = 4,3 [P.I.(PMs de partida) = 2,9]. TEM: particulas magneticas esfericas de tamano comprendido entre 190-270 nm. 49
/=\ N -N N H y N. Br—Pd—Br 0 PMC(A)II2 Ejemplo 36. Preparacion de PMC(A)I13. 5 Las PMC(A)113 se prepararon como se ha descrito para PMC(A)111 en el Ejemplo 34, pero utilizando el complejo 11(A)3 descrito en el Ejemplo 24. Se obtuvieron como un sOlido pulverulento de color marrOn, que se conserve) a 5 °C dispersadas en 1 mL de Tx 0,21%. ICP-MS: 0,36 %w Pd. IR (KBr): v 2900-3000 (m, arC-H st), 1723 (C=0 st), 1601 (m, arC=C st), 1493 (s, C=N st), 1450-1480 (m, arC=C st), 1260 cm-1 (C-N St (amida)). pH en 10 el punto isoelectrico del potencial Z: P.;. = 4,6 [P.I.(PMs de partida) = 2,9]. TEM: particulas magneticas esfericas de tamario comprendido entre 180-250 nm. N N . H y s'Pr2Ph Br—Pd—Br H lPr2Ph N PMC(A)II3 15 Ejemplo 37. Preparacion de PMC(A)1114. Las PMC(A)1114 se prepararon como se ha descrito para PMC(A)111 en el Ejemplo 34, pero utilizando el complejo 111(A)4 descrito en el Ejemplo 27. Se obtuvieron como un sOlido pulverulento de color marron, que Sc conservO a 5 °C dispersadas en 1 mL de Tx 20 0,21%. ICP-MS: 0,81 %w Pd. IR (KBr): v 2923-2970 (m, arC-H st), 1698 (C=0 st), 1601- 1650 (m, arC=C st), 1538 (s, C=N st), 1450-1480 (m, arC=C st), 1272 cm-1 (C-N St (amida)). pH en el punto isoelectrico del potencial Z: P.I. = 6,2 [P.I.(PMs de partida) = 2,9]. TEM: particulas magneticas esfericas de tamaiio comprendido entre 190-250 nm. 50
_ _ e HN—\N.,- 1 2 Br, )—N ? Pd > (7. 0_ Br' )--N /---N. HN—/ 0 PMC(A)III4 Ejemplo 38. Ensayos de actividad catalitica de las PMCs de esta invencion en reacciones de Suzuki-Miyaura. 5 Los ensayos cataliticos se Ilevaron a cabo dentro de una caja de guantes ("La petite" modelo 815-PGB de Plaslabs INC), en ausencia de oxigeno, en viales esterilizados tipo Eppendorf de 1,5 mL de un solo uso que contenian 1 mL de una suspensiOn del catalizador soportado de paladio(ii) en una mezcla 9:1 de una disoluciOn acuosa de 10 TritOnrm X405 at 0,21% en volumen y TM:, el haloareno correspondiente (4-bromo o 4- clorotolueno), acid° fenilboronico (relacion molar con respecto at haloareno 1:1,2), carbonato potasico (relacion molar con respect° al haloareno 1:3) y naftaleno como patron interno (0,5 mmol). En todos los casos se utilizaron 2,5 mg de PMCs y las cantidades de los sustratos se ajustaron para alcanzar una carga de paladio de 0,05 15 mol% [Pd] para las PMC(S1)11-3 descritas en los Ejemplos 28 a 30 y de 0,024 mol% [Pd] para el resto descritas en los Ejemplos 31 a 37, con respeto at haloareno. Estas mezclas se sonicaron en un ban° durante un minuto (Elmasonic S40, frecuencia de sonicaci6n de 37 kHz). Seguidamente los viales se colocaron dentro de la caja de guantes en el soporte de un agitador mecanico previamente termostatizado (Bioshake iQ de Qlnstruments) con 20 el control de temperatura a 65 °C para la activaciOn de bromotolueno y a 80 °C para la activacion de clorotolueno. Una vez colocados los viales, se comenzo a medir el tiempo de reacci6n. El avance de la reaccion se sigui6 retirando periodicamente muestras que se analizaron por cromatografia de gases (cromatografo HP-5890 Series II Instrument con detector por ionizaciOn de llama (FID); columna capilar polar DB-WAX con una pelicula 25 de polietilenglicol de 0,25 pm de grosor y de 30 metros de longitud y 0,25 mm de diametro; inyector a 250 °C, detector a 260 °C, isoterma en horno a 180 °C (bromotolueno) o isoterma a 120 °C durante 5 min y rampa de temperatura a 60°C/min hasta 200 °C (clorotolueno). Para el seguimiento por GC-FID se cogiO 1 pL de la 51
disolucion y se diluye) en el disolvente de reacciOn hasta 10 pL, de ahi se tome) 1 pL que se inyect6 directamente. La conversiOn se determine) a partir de la concentraci6n de haloareno presente en la mezcla de reaccion, utilizando el pico de naftaleno como patr6n interno y respect° a la recta de calibrado determinada para 4-yodotolueno. El producto de 5 acoplamiento fue identificado por RMN 1H. Todos los experimentos se realizaron at menos por duplicado. Tambien se realizaron blancos de la reacciOn, sin adicionar PMCs, para descartar posibles resultados falsos provocados por la contaminacion de paladio de los sustratos, bases, disolventes o de las PMs de partida sin complejo soportado. La Tabla 3 recoge los resultados obtenidos con las PMCs descritas en los Ejemplos 28 a 37. 10 Ejemplo 39. Ensayos de actividad catalitica de las PMCs de esta invencion en reacciones de Heck-Mizoroki. Los ensayos cataliticos se Ilevaron a cabo del modo descrito en el Ejemplo 38, pero con 15 4-yodotolueno, acrilato de metilo (relaciOn molar con respecto at haloareno 1:1,2), trietilamina (relacion molar con respecto at haloareno 1:1) y naftaleno como patr6n interno (0,5 mmol), con el agitador mecanico termostatizado previamente a 90 °C y con el cromat6grafo configurado como se ha indicado en el Ejemplo 38 para 4-bromotolueno. La Tabla 4 recoge los resultados obtenidos con las PMCs descritas en los Ejemplos 28 a 37 20 Ejemplo 40. Evaluacion de la reciclabilidad de las PMCs de esta invencion en reacciones de acoplamiento de Suzuki-Miyaura y de Heck-Mizoroki. Una vez terminada la reacciOn, se colocaron los viales dentro del campo magnetic° de un 25 iman de neodimio (Supermagnete) durante 5 min con el fin de las PMCs quedasen depositadas en el lado del Eppendorf oriented° hacia el iman. Posteriormente, se decantaron las disoluciones con los productos y las PMCs resultantes se lavaron con THF (5 x 1 mL) y Tx (5 x 1 mL; Tx = disolucion acuosa de TritonTm X405 at 0,21%v). A continuacion, sobre el vial con las MNPs recuperadas se adicion6 1 mL de Tx/THF (9:1) 30 que contenia una nueva mezcla de sustratos con el fin de restablecer las concentraciones iniciales de la reacci6n descritas en cada caso en los Ejennplos 38 y 39. Una vez se adicionaron los reactivos, se procedie) COMO se ha indicado en cada caso en los Ejemplos 38 y 39. La operaci6n se repitiO una docena de veces (13 usos del catalizador contando la reaccion inicial) siempre en las mismas condiciones y mismo tiempo de reacci6n. De la 35 Figura 4 a la Figura 6 se muestra una selecciOn de representaciones graficas de algunos de los perfiles cineticos obtenidos para las PMC(Si)112 descritas en el Ejemplo 32, 52
PMC(A)II3 descritas en el Ejemplo 36 y PMC(A)III4 descritas en el Ejemplo 37 en las reacciones de Suzuki-Miyaura tanto con el 4-bromotolueno como con el 4-clorotolueno que fueron Ilevadas a cabo como se describe en el Ejemplo 38. La Figura 7 y la Figura 8 muestran una selecciOn de representaciones graficas de algunos de los perfiles cineticos 5 obtenidos para las PMC(Si)I3 descritas en el Ejemplo 30, PMC(Si)112 descritas en el Ejemplo 32, PMC(A)113 descritas en el Ejemplo 36 y PMC(A)III4 descritas en el Ejemplo 37 en las reacciones de Heck-Mizoroki con el 4-yodotolueno que fueron Ilevadas a cabo como se describe en el Ejemplo 39. 10 Ejemplo 41. Cuantificacion del lixiviado de paladio de las PMCs de esta invencion en reacciones de acoplamiento de Suzuki-Miyaura y de Heck-Mizoroki. Se han realizado analisis cuantitativos de paladio mediante ICP-MS (Espectrometria de masas con fuente de plasma acoplado inductivamente) de las disoluciones separadas 15 tanto en las reacciones iniciales descritas en los Ejemplos 38 y 39 como en las sucesivas reacciones en las series de reciclados descritos en el Ejemplo 40. Los analisis se realizaron de las disoluciones separadas despues del primero (reciclado n° 0-1), del segundo (reciclado n° 1-2), del tercero (reciclado n° 2-3), del cuarto al duodecimo combinadas (reciclado n° 3-11) y del decirno tercer uso del catalizador (reciclado n° 12). 20 El contenido de paladio de las PMCs recuperadas al final de cada serie de reciclados tambien fue cuantificado mediante ICP-MS. En la cuantificaci6n de paladio mediante ICP-MS se han realizado como minim° 3 analisis independientes, en un Equipo 7700x Agilent (limite de detecciOn 1ppb (pg/L); modo de inyeccion de muestra: Helio 4,3 mL/minuto; valores aceptados [RSD] menores del 10%). Las muestras se prepararon tomando una 25 fracciOn de masa conocida del solid° obtenido por evaporacion directa de la suspensi6n o disoluciOn correspondiente y disolviendola en medio acidificado (acid° nitrico/acido clorhidrico 3:1). La Tabla 5 recoge una selecciOn ilustrativa del porcentaje de paladio inicial encontrado en las disoluciones separadas y del perdido por algunas de las PMCs de esta invenciOn (concretamente las PMC(Si)I12 descritas en el Ejemplo 32, las 30 PMC(A)II3 descritas en el Ejemplo 36 y las PMC(A)III4 descritas en el Ejemplo 37) en las reacciones de Suzuki-Miyaura iniciales y sucesivas reutilizaciones descritas en los Ejemplos 38 y 40, respectivamente, junto a los descensos de conversion (medida en cada caso siempre al mismo tiempo de reacciOn) registrados en las reacciones consecutivas de cada serie y expresados en puntos porcentuales. La Tabla 6 recoge una 35 seleccion ilustrativa del porcentaje de paladio inicial encontrado en las disoluciones separadas y del perdido por algunas de las PMCs de esta invencion (concretamente las 53
PMC(S1)13 descritas en el Ejemplo 30, las PMC(Si)112 descritas en el Ejemplo 32, las PMC(A)II3 descritas en el Ejemplo 36 y las PMC(A)III4 descritas en el Ejemplo 37) en las reacciones de Heck-Mizoroki iniciales y sucesivas reutilizaciones descritas en los Ejemplos 39 y 40, respectivamente, junto a los descensos de conversion (medida en 5 cada caso siempre al mismo tiempo de reacciOn) registrados en las reacciones consecutivas de cada serie y expresados en puntos porcentu ales. Ejemplo 42. Determinacion de los valores de productividad y actividad iniciales (TON° y TON, de productividad acumulada (TON,-) de actividad promedio (TOFAv) Y 10 de contenido de paladio encontrado en los productos (en ppm masa) utilizando las PMCs de esta invencion en reacciones de acoplamiento de Suzuki-Miyaura y de Heck-Mizoroki. Los valores de TON° se han determinado teniendo en cuenta la relacion molar del 15 sustrato limitante con el paladio incorporado con cada PMC y la conversion alcanzada al tiempo especificado en cada caso (Tabla 7 a Tabla 9), en las reacciones descritas en los Ejemplos 38 y 39. El valor de TOF0 para cada PMCs es la relaciOn entre el correspondiente valor de TON() y el tiempo, expresado en horas, para alcanzar esa productividad en las reacciones descritas en los Ejemplos 38 y 39. El valor de TONT para 20 cada PMCs es el sumatorio del valor de TON() y los valores TON registrados en cada una de las 12 reutilizaciones descritas en el Ejemplo 40. El valor de TOFAv para cada PMCs es la media aritnnetica del TOF0 y los valores TOF registrados en cada una de las 12 reutilizaciones descritas en el Ejemplo 40. El contenido de paladio en los productos tras los 13 usos de cada PMC se ha determinado teniendo en cuenta el valor de TONT 25 alcanzado en cada caso, el peso molecular del producto obtenido, la cuantificaciOn descrita en el Ejemplo 41 del lixiviado del metal a las disoluciones separadas de las PMCs en los reciclados descritos en el Ejemplo 40 y la carga metalica inicial utilizada en cada serie. El contenido de paladio en los productos se expresa en partes por millOn (ppm) como la relacion de masas de metal encontrado en las disoluciones y del producto 30 total formado. La Tabla 7 recoge los valores encontrados en las reacciones de Suzuki-Miyaura con 4-bromotolueno para algunas de las PMCs de esta invencion, concretamente las PMC(Si)I11-3, PMC(A)I11-3 y PMC(A)1114 descritas en los Ejemplos 31 a 37. La Tabla 8 recoge los valores encontrados en las reacciones de Suzuki-Miyaura con 4-clorotolueno para algunas de las PMCs de esta invenciOn, concretamente las 35 PMC(Si)111-3, PMC(A)I11-3 y PMC(A)1114 clescritas en los Ejemplos 31 a 37. La Tabla 9 recoge los valores encontrados en las reacciones de Heck-Mizoroki con 4-yodotolueno 54
para las PMCs descritas en los Ejemplos 28 a 37. Ejemplo 43. Ana!Isis TEM de las PMCs de esta invencion y de las disoluciones separadas con los productos cataliticos. 5 Se han inspeccionado mediante TEM (Microscopia Electronica de Transmisi6n) las PMCs de esta invenciOn descritas en los Ejemplos 28 a 37, tanto antes de su uso en los ensayos de actividad descritos en los Ejemplos 38 y 39 como de las PMCs recuperadas al finalizar las series de reciclados descritos en el Ejemplo 40, asi como de muestras 10 preparadas a partir de las disoluciones separadas en esos mismos reciclados. Los analisis TEM se han realizado empleando un microscopio JEOL JEM 2100 que opera a un voltaje de 200 kV, equipado con porta muestras de doble inclinaciOn ±42/±300, con una resolucion entre puntos de 2,5 A y un sistema de microanalisis EDS ("x-ray energy dispersive spectrocopy") con un instrumento OXFORD INCA. Alternativamente se ha 15 utilizado un microscopio HITACHI H7650 que opera a un voltaje de 120 kV, equipado con una camara GATAN de 11 Mpx de resoluciOn. Se siguieron dos procedimientos distintos de preparaciOn de muestras de PMCs en funci6n del equipo utilizado para la medida. Para el equipo JEOL JEM 2100, se embebieron unos miligramos de las PMCs correspondientes en una resina epoxidica de baja viscosidad conocida coma Spurr, que 20 consta de cuatro componentes: la resina propiamente dicha (ERL 4206, 50 mL), plastificante (DER 736, 30 mL), endurecedor (NSA, 130 nnL) y acelerador (DMAE, 2 mL). Se dej6 curar y endurecer la resina durante dos dias, tras lo cual se procedi6 a cortarla en laminas muy finas mediante el uso de un ultramicrotomo (Reichert-Jung, modelo Ultracut-E.). Estas laminas se depositaron sobre rejillas de cobre de 3 mm de diametro 25 recubiertas de carbono (400 mesh). Alternativamente para el microscopio HITACHI H7650, la preparacion de las muestras se realize) preparando dispersiones de las PMCs en metanol o agua (5-10 pL, 0,25-0,5 rng/nnL) sobre rejillas de cobre de 3 mm de diametro recubiertas de carbono (400 mesh) dejando que se produzca la deposici6n por evaporacion. Las muestras de las disoluciones cataliticas separadas de las PMCs se 30 analizaron indistintamente en uno de los dos equipos y su preparacion se realizo adicionando 5 gotas de la disolucion de catalisis sobre rejillas de cobre de 3 mm de diametro recubiertas de carbono (400 mesh) dejando que se produzca la deposiciOn por evaporaciOn. La ausencia de paladio metalico en las muestras fue determinada por EDS, inspeccionando la existencia de las lineas caracteristicas de emisi6n de la capa L de este 35 metal a 2,83 KeV (Lai) y 3,03 KeV (431). La comparaci6n y analisis de las imagenes obtenidas de las PMCs, enteras o cortadas con ultramicrotomo, antes y despues de su 55
5 10 utilizacion en catalisis como se describe en los Ejemplos 38, 39 y 40, permite comprobar que ninguna sufren cambios morfologicos apreciables y que no se observan agregados de paladio metalico junto a ellas ni en las muestras preparadas a partir de las disoluciones separadas con los productos al final de cada reacci6n. BIBLIOGRAFIA "Guideline on the Specification Limits for Residues of Metal Catalyst or Metal Reagents", European Medicines Agency, 2008, Doc. Ref. EMEA/CHMP/SWP/4446/2000. de Vries, J. G. "Palladium-Catalysed Coupling Reactions", Top. Organomet. Chem. 2012, 42, 1-34. Diez-Gonzalez, S.; Marion, N.; Nolan, S. P. "N-Heterocyclic Carbenes in Late Transition 15 Metal Catalysis", Chem. Rev. 2009, 109, 3612-3676. Baig, R. B. N; Varma; R. S. "Magnetically retrievable catalysts for organic synthesis", Chem. Commun. 2013, 49, 752-770. 20 Shylesh, S.; Schunemann, V.; Thiel, W. R. "Magnetically Separable Nanocatalysts: Bridges between Homogeneous and Heterogeneous Catalysis", Angew. Chem. Int. Ed. 2010, 49, 3428-3459. Stevens, P. D.; Li, G.; Fan, J.; Yen, M.; Gao, Y. "Recycling of homogeneous Pd catalysts 25 using superparamagnetic nanoparticles as novel soluble supports for Suzuki, Heck, and Sonogashira cross-coupling reactions", Chem. Commun. 2005, 4435-4437. Zheng, Y; Stevens, P. D.; Gao, Y. "Magnetic Nanoparticles as an Orthogonal Support of Polymer Resins: Applications to Solid-Phase Suzuki Cross-Coupling Reactions", J. Org. 30 Chem. 2006, 71, 537-542. 35 Stevens, P. D.; Li, G.; Gardimalla, H. M. R., Yen, M.; Gao, Y. "Superparamagnetic Nanoparticle-Supported Catalysis of Suzuki Cross-Coupling Reactions", Org. Lett. 2005, 7, 2085-2088. Yang, H.; Li, G.; Ma, Z. "Magnetic core—shell-structured nanoporous organosilica 56
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5 10 Borja, G.; Monge-Marcet, A.; Pleixats, R.; PareIla, T.; Cattoen, X.; Wong Chi Man, M. "Recyclable Hybrid Silica-Based Catalysts Derived from Pd—NHC Complexes for Suzuki, Heck and Sonogashira Reactions", Eur. J. Org. Chem. 2012, 3625-3635. Berardi, S.; Carraro, M.; Iglesias, M.; Sartorel, A.; Scorrano, G.; Albrecht, M.; Bonchio, M. "Polyoxometalate-Based N-Heterocyclic Carbene (NHC) Complexes for Palladium-Mediated C—C Coupling and Chloroaryl Dehalogenation Catalysis", Chem. Eur. J. 2010, 16, 10662-1066. Kunze, K.; Nyce, G.; Guo, W. "Methods of polymerizing silanes and cyclosilanes using N-heterocyclic carbenes, metal complexes having N-heterocyclic carbene ligands, and lanthanide compounds", PCT Int. Appl. 2011, PCT/US2011/046155, W02013019208A1. 15 Diez-Barra, E.; de la Hoz, A.; Sanchez-Migallon, A.; Tejeda, J. "Phase transfer catalysis without solvent. Synthesis of bisazolylalkanes", Heterocycles 1992, 34, 1365-1373. Organ, M. G.; O'Brien, C. J.; Kantchev, E. A. B. "Transition metal complexes of N-heterocyclic carbenes, method of preparation and use in transition metal catalyzed 20 organic transformations", CA Appl. 2007, C,A2556850A1). 25 Yang, H.; Han, X.; Li, G.; Yunwei Wang, Y. "N-Heterocyclic carbene palladium complex supported on ionic liquid-modified SBA-16: an efficient and highly recyclable catalyst for the Suzuki and Heck reactions", Green Chem. 2009, 11, 1184-1193. Polshettiwar, V.; Varma, R. S. "Pd—N-heterocyclic carbene (NHC) organic silica: synthesis and application in carbonecarbon coupling reactions", Tetrahedron 2008, 64, 4637-4643. Corma, A.; Gonzalez-Arellano, C.; Iglesias, M.; Perez-Ferreras, S.; Sanchez, F. 30 "Heterogenized Gold(I), Gold(III), and Palladium(II) Complexes for C—C Bond Reactions", Syntleff 2007, 1771-1774. Lee, S.-M.; Yoon, H.-J.; Kim, J.-H.; Chung, W.-J.; Lee, Y.-S. "Highly active organosilane-based N-heterocyclic carbene-palladium complex immobilized on silica particles for the 35 Suzuki reaction", Pure App!. Chem. 2007, 79, 1553-1559. 58
Karimi, B.; Enders, D. "New N-Heterocyclic Carbene Palladium Complex/Ionic Liquid Matrix Immobilized on Silica: Application as Recoverable Catalyst for the Heck Reaction", Org. Lett. 2006, 8, 1237-1240. 5 Wang, H. M. J.; Lin, I. J. B. "Facile Synthesis of Silver(I)-Carbene Complexes. Useful Carbene Transfer Agents", Organometallics 1998, 17, 972-975. Rosario-Amorin, D.; Gaboyard, M.; Clerac, R.; Vellutini, L.; Nlate, S.; Heuze, K. "Metallodendritic Grafted Core—Shell y-Fe20— Nanoparticles Used as Recoverable 10 Catalysts in Suzuki C—C Coupling Reactions", Chem. Eur. J. 2012, 18, 3305-3315 59
COMPLEJOS NHC DE PALADIO HETEROGENEIZADOS Y SUS USOS COMO CATALIZADORES RECUPERABLES SECTOR DE LA TECNICA 5 La invenciOn se ennnarca el sector quimico y farmaceutico, mas concretamente sobre catalizadores para procesos de sintesis organica basados en complejos metalicos, y mas especificamente en complejos carbeno N-heterociclico de paladio soportados, separables magneticamente tras su uso, reutilizables y resistentes al lixiviado metalico, y en su uso 10 en reacciones de acoplamiento carbono-carbono. ESTADO DE LA TECNICA Como consecuencia del facil acceso de los sustratos a sus centros activos y al entorno 15 modificable y controlable de estos, los catalizadores basados en complejos metalicos se caracterizan por su elevada actividad y selectividad en multitud de procesos quimicos que se Ilevan a cabo en condiciones suaves en fase homogenea. Sin embargo, en la actualidad el uso industrial de la catalisis homogenea aplicado a la producci6n de farmacos, agroquimicos y otros productos de la quimica fina, es bastante limitado. Las 20 razones principales de lo anterior son, por un lado, el coste de los complejos y, por otro, la mayor dificultad para separarlos de los productos comparada con catalizadores heterogeneos. Estos obstaculos son especialmente relevantes con complejos de metales del grupo del platino (Pt, Pd, Ir, Rh, Os, Ru), sobre los que, edemas, existen directrices y regulaciones ambientales y sanitarias que restringen drasticamente los niveles 25 permisibles de contaminaciOn por metales en muchas producciones (e.g., European Medicines Agency 2008). Existe, por tanto, un enorme mercado potencial para catalizadores metalicos que aCinen las ventajas de los catalizadores de fase homogenea (i.e., alta actividad y selectividad en 30 condiciones suaves) con las de los de fase heterogenea (i.e., elevada productividad y facil recuperaci6n y reciclado). Una clasificaciOn general de las estrategias que hasta ahora se han explorado para ello comprende: catalisis multifasica o confinamiento del catalizador homogeneo en una fase distinta a la de sustrato y productos, incluyendo fases acuosas, liquidos ionicos, fluidos supercriticos o disolventes fluorados; ii) utilizaciOn de 35 membranas de nanofiltracion con catalizadores de peso molecular agrandado mediante su inmovilizaciOn a soportes solubles coma dendrimeros, polinneros o polisisesquioxanos; 2
and iii) heterogeneization or immobilization of soluble metal complex to insoluble supports, both organic and inorganic. In general, these attempts have not resulted in commercially viable processes for various reasons, finding that the most frequent are the leachate of the active center and / or its degradation, which result in the metal contamination of the products and / or fatal losses of productivity, activity and selectivity. The particular case of palladium, known for its usefulness in catalyzing a wide range of transformations in organic synthesis, conventionally associated with organophosphorus ligands, is no exception: very few industrial processes are implemented in which their soluble complexes (de Vries) are involved. J. G. 2012) and in them it has generally been necessary to develop specific and expensive procedures to eliminate metallic and phosphorus toxic residues. Segan de Vries, in the five years prior to 2012, only 6-7% of the synthetic stages of the pharmaceutical industry 15 involved homogenous catalysis, highlighting that 50% of them corresponded to the most recently introduced drugs. It would therefore be desirable to have catalysts, in particular palladium and phosphorus-free ligands, that combine a distinctive behavior with high values of 20 TON (of the English turnover number), with which to arrive to implement "clean productions" in which they can be separated easily and efficiently, making it possible to reuse them, or use them continuously, and in which the expensive operations of metal purification of the products can be dispensed with. 25 Some ligands that have recently appeared as a very attractive alternative to organophosphates are those of the N-heterocyclic carbine (NHC) type. NHCs provide strong bonds, which result in very robust and excellent metal complexes to catalyze a very wide range of processes in the homogeneous phase, in which the stereo-electronic characteristics of the ligand play an important stabilizing role 30 (Diez-Gonzalez, S. , etal. 2009). To immobilize metal catalysts, among other supports currently available, magnetic nanoparticles (NPMs) have been used with various types of ligands covalently anchored to the surface, (Baig, R. B. N. , et al. 2013; Shylesh, S. , et al. 35 2010). There are also descriptions in which heterogeneized NHC palladium complexes have been used through alkylsilOxide groups on bare NPMs 3
(Stevens, P. D. , et al. Chem Commun. 2005; Zheng, Y. , et al. 2006), through benzyl groups on polystyrene coated NPMs (Stevens, P. D. , et al. Org. Lett. 2005), and arylsiloxane groups on magnetic microspheres (Yang, H. , et al. 2012) or silicon coated NPMs (Yang, H. , et al. 2011). All of them have been shown to be active in various cross-coupling reactions (i. and. , Suzuki-Miyaura, Heck-Mizoroki and Sonogashira), are magnetically recoverable and most have been reused. Of the above only in one case (Yang, H. , etal. 2011) the content of palladium in the products has been determined, but only after the first use of the catalyst. In all of them, the metal complex support procedure follows the sequence: 1) support functionalization with imidazolium salts, which are precursors of NHC ligands; 2) metalation of the previous functionalized support with acetylacetonate or palladium acetate aPd (acac) 2] 6 [Pd (OAc) 2]). The disadvantage of this methodology, which on the other hand is the usual one with any type of support and ligand, is the impossibility of being able to control both the formation of corrplejos with a unique coordination environment, 15 as well as the presence of adsorbed and non-anchored metal remains covalently In this sense, recently it has been found that, using silica gel as a support, the catalytic results are much better when the NHC complex of preformed palladium is immobilized than when it is synthesized on the surface of the silica gel (Tyrrell, E. , etal. 2011). The present invention proposes the preparation of new palladium NHC complexes (CPs) and their subsequent heterogeneization on iron oxide magnetic particles (PMs), together with their use in cross-coupling reactions. The method provides metallic species (bier, defined micas, in which NHC ligands strongly fix the metallic centers and protect them during catalysis, while being covalently supported through inert "Y" groups to particles coated with a material also inert, while the superparamagnetism of the nude ° of the particle to which they are associated allows its separation from the medium by applying a magnetic field °. These magnetic particles with the supported catalysts (PMCs) give rise to stable dispersions in water, catalyze carbon-carbon coupling reactions in aqueous medium under mild conditions, even with aryl chlorides, recover without degradation by simple magnetic separation, can be reuse Arriving at very high TON values and do not suffer metallic leaching. Concerning NHC ligand precursors substituted by terminal complementary groups (Gc) and the like or necessary to synthesize CPs of types I-111, 4 has been described.
an imidazolium salt substituted with a protected amine in the form of a phthalimido group (Harjani, J. R. , et al. 2008), three others substituted with a primary amine as a complementary group "G" (Busetto, L. et al. 2008; Ballarin, B. , et al. 2012; Ohara, H. , et al. 2012), another five in which this group is triethoxysilyl (Chi, Y. S. , et al. 2004; Trilla, M. , et 5 al. 2009; Borja, G. , et al. 2012, Berardi, S. , et al. 2010) and five others in which it is trimethoxysilyl (Kunze, K. , et al. PCT / US2011 / 046155, Tyrrell, E. , et al. 2011). As precursors necessary for the synthesis of type III complexes, the synthesis of bis (azolyl) alkanes (Ten-Bar, E, etal) have been described. Heterocycles 1992, 34, 1365-1373). A single example of mono CP (NHC) related to the formulation of type I is known, specifically with the NHC ligand substituted by a chain with a "G '= triethoxysilyl (Borja, G. , etal. 2012), although other related complexes have been described but without this type of substitution (Organ, M. G. , et al. CA2556850A1). 15 Bis CPs (NHC) have been described with the structure referred to as type II in which the "G" is trialkoxysilyl, using similar procedures (Kunze, K. , et a /. PCT / US2011 / 046155; Tyrrell, E. , etal. 2011; Berardi, S. , etal. 2010), or different (Yang, H. , et al. 2009; Polshettiwar, V. , et al. 2008; Corma, A. , et al. 2007; Lee, S. -M. , et al. 2007, 79; Karimi, B. , et al. 2006), to employees in the context of the present invention. In 20 series as similar procedures, the synthesis is performed through intermediate silver complexes, which are prepared following the standard method described by Lin (Wang, H. M. J. , et al. 1998), but in no case are these carbine transfer agents isolated, purified and characterized, unlike the procedure proposed in the present invention. No type III CP with 25 alkoxysilyls has been described as "G", nor are there known of the types referred to herein as II and III in which that group is a primary amine, although both palladium complex topologies, chelate or not, they are abundant in the bibliography. Procedures for supporting preformed CPs of types I and II already referred to have been described (i. and. , Gc = Si (OR) 3) on silicas of different nature, or to incorporate them in composite materials by means of sol-gel condensations, but in no case to generate PMCs. As mentioned, if functionalized PMCs have been prepared with NHCs precursors immobilized to? Saves alkoxysilyl groups on different supports that have subsequently been metalated with a source of palladium, but none on magnetic particles coated with silica of any kind, existing an example of fixing to this type of materials through arylsiloxane bonds as precedent plus 5
nearby (Yang, H. , 2011). In all of them the immobilization procedure used prevents knowing the identity and structural uniformity of the supported complexes. Finally, a procedure for supporting palladium phosphan-type dendritic complexes 5, with a primary amine at the dendrOn focal point, on polymer-coated PMs with "carboxylic acid groups" such as "Gs" (Rosario-Amorin, D) . , et al. 2012). The PMCs based on NHC ligands mentioned, although with a 10-entomb structure of the indeterminate palladium, have proven to be active in various cross-coupling processes under various reaction conditions, are magnetically recoverable and most have been reused. Only in one case (Yang, H. , 2011) the leaching of palladium to the products has been determined and only after the first use of the catalyst. DESCRIPTION OF THE INVENTION The present invention comprises a method of preparing new CPs that, once formed, can be heterogeneized on PMs, providing PMCs with 20 well-defined Palladium species. The PMCs are characterized by giving rise to stable dispersions in water, they are active in catalytic processes of formation of carbon-carbon bonds in aqueous medium and in mild conditions, the superparamagnetism of the nixie ° of the particles allows their separation of the products by applying a field Magnetic, recover without degradation, can be reused by reaching very high TON values and do not undergo metallic leaching, or is insignificant, resulting in products of the catalysis with palladium contents below 10 ppm by mass (up to levels of about ppb) after the magnetic separation of the particles. 30 In a first aspect, the invention is related to new CPs that have typologies I, II and III. 35 In a second aspect, the invention is related to the synthetic methods of said CPs of types I, II and III and their precursors. In a third aspect the invention is related to the procedures of
immobilization of these CPs of types I, II and III on magnetic particles (PMs) of iron oxide to generate magnetic particles with the supported complexes (PMCs). In a fourth aspect, the invention is also related to the use of said PMCs 5 as catalysts for carbon-carbon coupling reactions, and their characteristics in relation to their separation of products, their reuse, their productivity and their high resistance to degradation. and the leachate. 10 PM CP PMC DETAILED DESCRIPTION OF THE INVENTION Specifically, the invention comprises the synthesis of CPs with NHC 15 ligands substituted by complementary groups (Gc) terminal of an alkyl chain and useful for the formation of a covalent bond "Y" to the support, the post-synthetic immobilization of complexes to PMs that have a coating containing surface groups (Gs) suitable to form the "Y" anchor, and the use of these PMCs in catalysis-recovery-reuse cycles in halide activation reactions of aryl Specifically, the CP to be supported comprises mono (NHC), bis (NHC) and bis (NHC) -chelate complexes, in which "L" is a neutral monodentate ligand L 'with donor nitrogen (type I), preferably a pyridine , and "R" is an alkyl or aryl or alkylaryl substituent, or "L" is another NHC anchor ligand with the same "R" (type II), or "L" is another NHC anchor ligand in which "R" it is a bridge alkyl chain between the two NHC ligands (type III), respectively. In them "X" is a monoaniOnic substituent, preferably a halide, and "Gc" is a functional group capable of undergoing condensation reactions, preferably a trialkoxysilyl or primary amine, which is located at the end of an alkyl carbon chain, preferably between 1 and 4. Particularly, in the chelate CPs (type III) the heterocyclic rings are linked through an n-link alkyl chain, preferably between 1 and 3. 7
Gc NN and 'FR X-Pd-X L' Gc, opy N X-Pd-X R NN GC Pd A 'Gc "(x' \ X Th-Gc The PMs used in support are commercially available and characterized by 5 diameters in the range of tens to hundreds of nanOmeters, preferably 100-500 nm, for a nixie ° of an iron oxide, preferably maghemite, and for an inert coating such as silica or polystyrene functionalized with "Gs", preferably silanoles and acids carboxylic, respectively. Additionally, the immobilization process consists of condensation reactions, preferably with formation of siloxane or amide groups, between the CPs and the corresponding PMs dispersed in organic solvents, or preferably in an aqueous medium in the presence of small amounts of non-ionic surfactants. 15 ftal, N-T. N kin INH2NH 2 (CH3) 2CHOH N 2 PdX2 / K2CO31L 'CH2Cl2 Ag20 / = \ N LN / I-ZzN fta1. 14, X, A X - X- tv \ THF CH3CN ftall- / n tr ftal (R'0) 3Sii + X CH2Cl2 (R'0) 3S1 N. R X-Pd-X L 'I (Si) P = 1 N -ny AgX 3 [PdX2 (L "2)] \ in X-Pd-X CH2Cl2 R -1 \ 1" tNN4Gc 8 II 4 1 Pd (OAc ) 2 DMS0 NLN Pd tIal-An X / \ X kftal 5 NH 2 NH2I CH3CN Nk H2N45Pd n X / \ X (N1-12 III (A)
The present invention also concerns the uses of the PMCs of the invention in carbon-carbon coupling reactions, particularly Heck-Mizoroki and Suzuki-Miyaura with aryl halides, dispersed in an accusing medium and in mild conditions, and their reuse in catalysis after its effective separation of the products by means of an external magnet. The synthesis of some of the CPs of this invention that have formulas of types I, ll and Ill can be achieved by the transformations indicated in the previous scheme. The especially preferred ester complexes described in the examples of this invention and the methods for preparing the complexes of the I-Ill types and their intermediates consist of: a) transforming N-substituted imizarles preferably, but not exclusively, non-substituted heterocyclic carbon in position 2, by reactions of N-15 alkylation with N- (haloalkyl) phthalimides, to form and isolate salts of imidazolium 1 with protected primary amines in the form of phthalimido (phthalic) group, 1 20 where R may be a alkyl, aryl or alkylaryl group, containing between 1 and 20 carbon atoms, and may be substituted by groups without active protons (halogen, sulfonate, carboxylate, ether, floater, ketone, sulfoxide, ester, amide, nitrile); where alternatively R may be another chain with the phthalimido group; where X-can be an aniOnic species, preferably a halide; and where the spacer between the protective group and the heterocycle is defined by a chain length of n links that can be comprised between 1 and 4 carbons. b) N-substituted N-substituted transformer, preferably, but not exclusively, non-substituted in heterocyclic carbon at position 2, by reactions of N-30 alkylation with (haloalkyl) trialkoxysilanes, to form and isolate imidazolium salts 2 (Si) with a trialkoxysilyl group, 9
(I: 110) 3 If N, R X-2 (Si) where R, X and n have been previously defined in transformation a); where alternatively R may be another chain with the trialkoxysilyl group; and where R '5 can be methyl or ethyl. c) transform the imidazolium 1 salts, by conventional procedures of Gabriel's synthesis (acidic or basic hydrolysis), or preferably by the Ing-Manske method using hydrazine, to formerly and isolate imidazolium salts 2 (A) with a 10 Primary chain terminal amine group, F ----- \ H2NNN. R 2 (A) where R, X and n have been previously defined in transformation a); and where alternatively R may be another chain with a terminal primary amine. d) transform the imidazolium 2 salts (Si), by a patented procedure (Organ, M. G. , etal. , CA2556850A1), to form and isolate mono complexes (NHC) of type 1 (81), in which the carbine ligand is coordinated, preferably but not exclusively, by its carbon 2, 1 = 1. (Fro) 3sii. . . ), NyN, R X -Pd- X L 'l (Si) where R, X and n have been previously defined in the transformed & a) and R' in the transformed &b); where natively the ligands X may independently be a halide, carboxylate, hydride, or an alkyl, allyl, aryl, alkylaryl, alkoxy, aryloxide, beta-diketonate, substituted or unsubstituted thiolate; and where L 'is a neutral monodentate ligand with nitrogen donor, preferably 10
a pyridine that can be substituted by alkyls or halides in any of its carbons. e) transform the imidazolium 2 salts (Si or A), by the standard procedure 5 described by Lin (Wang, H. M. J. , et al. 1998) with Silver Oxide, to form and isolate NHC complexes of silver 3 (Si or A), in which the carbine ligand is coordinated, preferably but not exclusively, by its carbon 2, 10 (R10) 3Si, / Ny N. R AgX 3 (Si) H2N. 0, nNyN R AgX 3 (A) where R, X and n have been previously defined in transformation a) and R 'in transformation b). f) transform the silver complexes 3 (Si or A), by reactions of transmetalation to palladium (ii) precursors with thousands ligands and of general formula [PdX2L "2] (L" 2 = ethylenediamine, N, N, N 'N'-tetramethylethylenediamine, 1,5-cyclooctadiene; or L "= benzonitrile, acetonitrile), to form and isolate bis (NHC) type II (Si or A) complexes, in which the carbene ligands are coordinated, preferably but not exclusively, for its carbon 2, 20 / = \ (R0) 3SiNyN, RX -Pd-X R 'NN / fiSi (OR') 3 II (Si) / = \ H2NNyN, RX -Pd- X R_Pk 'NN in NH2 11 (A) where R, X and n have been previously defined in transformed & a) and R 'in transformation b); and where alternatively the X ligands can independently be a halide, carboxylate, hydride, or an alkyl, allyl, aryl, alkylaryl, alkoxide, aryl oxide, beta-diketonate, substituted or unsubstituted thiolate. g) transforming bis (imidazolyl) alkanes, preferably but not exclusively, unsubstituted in the heterocyclic carbon in position 2, to form and isolate salts of 11
5 imidazolium 4 with protected primary amines in the form of a phthalimide (phthalyl) group by N-alkylation reactions with N- (haloalkyl) phthalimides, n 'f NrOn (% N 0 0 4 where X- yn have been previously defined in the transformation a) and the bridge between imidazolic rings is defined by a chain length of n 'links that can be between 1 and 3. 10 h) transform salts 4, by means of metalation reactions in the presence of palladium acetate, to form and isolate bis (NHC) chelate 5 complexes with a protected primary amine in the form of a phthalimide (phtal) group, in which the carbine ligands they are coordinated, preferably but not exclusively, by their carbon 2, and I \ 1 — Pd) N NAn Xj 15 5 where X- yn have been previously defined in transformation a) and n 'in transformation g); and where additionally the X ligands can independently be a halide, carboxylate, hydride, or an alkyl, allyl, aryl, alkylaryl, alkoxide, aryloxide, beta-diketonate, substituted or unsubstituted thiolate i) transform chelate complexes 5, by procedures Conventional methods of Gabriel's synthesis (acidic or basic hydrolysis), or preferably by the lng-Manske method using hydrazine, to form and isolate bis (NHC) chelate complexes of type III (A) with chain-terminating main amine groups, in which the carbene ligands are coordinated, preferably but not exclusively, by their carbon 2, 12
Pd H2N4j / n X / \ X kNH2 III (A) where X and n have been previously defined in transformation a) and n 'in transformation g); and where alternatively the X ligands can independently be a halide, carboxylate, hydride, or an alkyl, allyl, aryl, alkylaryl, alkoxide, aryl oxide, beta-diketonate, substituted or unsubstituted thiolate. With regard to the synthesis of PMCs of this invention, 10 condensation reactions between the Gs of the PMs and the corresponding Gc of the CPs of types I, II or III can be achieved. The PMs used as support are commercially available with a nude °, preferably but not limited to, of maghemite (y-Fe203) and are coated with silica or, alternatively, with polystyrene functionalized with carboxylic acid groups. Especially preferred PMCs are described in the examples of this invention and the methods for preparing them consist of: j) heterogeneizing the CPs of types I (Si) and II (Si) on silica coated PMs, by condensing the groups trialkoxysilyl of the corresponding CPs and surface silanol groups of the PMs, to form siloxane anchors and isolate the corresponding PMC (Si) I and PMC (Si) II, [Pd] [Pd] [Pd] [Pd] [Pd] [Pd] FeO. [Pd] [Pd] [Pd] [Pd] [Pd] [Pd] PMC (Yes) 1 0, O-Si N N'R 0 '1`);) and X — Pd-X L' l (Yes ) - anchored 13
[Pd] [Pd] [Pd] [Pd] [Pd] [Pd] PMC (Si) II / = \ 0-Sid x_Ny N —0 0 (1) 'X — Pd-X FOC) - II (Yes) - anchored where R, X and n have been previously defined in transformation a) and L "in transformation d); and where alternatively the X ligands can independently be a halide, carboxylate, hydride, or an alkyl, allyl, aryl, alkylaryl, alkoxide, aryl oxide, beta-diketonate, substituted or unsubstituted thiolate. The immobilization process comprises the dispersion of the PMs in organic solvents, or preferably in a hydroalcoholic medium in the presence of small amounts of non-ionic surfactants with high hydrophilic-hydrophobic balance (HLB> 15, used below their critical micellar concentration) , a slow addition of an alcoholic solution of the CP to be immobilized, a constant mechanical agitation and a washing sequence consisting of trapping the PMCs with an external magnet and separating them by decanting the solutions. The PMC (S1) 1 and 15 PMC (S1) 11 are characterized by palladium contents that correspond to about 1-4 CP molecules immobilized per nm2 of surface. Table 1 collects metal contents from the examples of especially preferred PMCs. Table 1 Palladium content in the PMC (Si) I and PMC (Si) II of the examples. at PMC (Si) In ° PMC (S1) 11 n °: 1 mg Pd / g MNPs 1.27% by weight of Pd 0.28 mmol Pd / g MNPs 0.026 (Molecules / nm2) ° 1.6 2 3 1 2 3 3.59 3.07 2.39 5.07 4.25 0.77 0.66 0.24 0.51 0.43 0.072 0.062 0.022 0.048 0.040 4.3 3.7 1.3 2.9 2.4 a Determined by ICP-MS. Relative Standard Deviations in quantifications s10%. For PMs of 300 nm, density of 2 g / cm3 and a specific surface area of 10 m2 / g. k) heterogeneize CPs of types II (A) and III (A) on PMs coated with 14
5 crosslinked polystyrene functionalized with carboxylic acid groups (density of COOH groups?. 300 pmol / g), by condensing the primary amine groups of the corresponding CPs and the surface acid groups of the PMs, to form amide anchors and isolate the corresponding PMC (A) II and PMC (A) III, [Pd] [Pd] [Pd] [Pd] [Pd] H / = \ NN 0 X -Pd- X 0 N N. RN "n H [Pd] [Pd] [Pd] [Pd] [Pd] [Pd] PMC (A) II [Pd] [Pd] [Pd] PMC (A) 111 [P '• [Pd] 11 ( A) - anchored NH OFIN X 'Pd (>) X /) --- N nri NH 111 (A) - anchored „,,,, 10 where R, X and n have been previously defined in transformation a) and n" in the transformation g); and where alternatively the X ligands can independently be a halide, carboxylate, hydride, or an alkyl, allyl, aryl, alkylaryl, alkoxy, aryloxide, beta-diketonate, substituted or unsubstituted thiolate. 15 The immobilization procedure is based on a modification of a described method (Rosario-Amorin, D. , et al. 2012) and includes the dispersion of PMs in a hydroalcoholic medium in the presence of small amounts of non-ionic surfactants with a high hydrophilic-hydrophobic balance (HLB> 15, used below their critical micellar concentration) in the presence of a carbodiimide as an agent of 20 coupling, the addition of a solution in a very polar solvent of the CP at 15
immobilize, a constant mechanical agitation and a sequence of washes that consists of trapping the PMCs with an external magnet and separating them by decanting the solutions. The PMC (A) II or PMC (A) III are characterized by palladium contents that correspond in tomb to 1-3 CP molecules immobilized per nm2 of 5 surface. Table 2 collects metal contents from the examples of especially preferred PMCs. Table 2. Palladium content in the PMC (A) II and PMC (A) III of the examples. a mg Pd / g MNPs ° A by weight of Pd mmol Pd / 9 MNPs (Molecules / nm2) ° PMC (A) IIn ° PMC (A) IIIn ° No: 1 2 3 4 2.58 5.38 3, 60 8.12 0.26 0.54 0.36 0.81 0.024 0.046 0.031 0.076 1.0 1.8 1.6 3.1 a Determined by ICP-MS. Relative Standard Deviations in quantifications s10%. For PMs of 200 nm, density of 2 g / cm3 and a specific surface area of 15 m2 / g. The essential characteristics of the PMCs of the present invention are that they catalyze 10 carbon-carbon coupling reactions under mild conditions, which are easily separated from the reaction medium, which can be reused in a series of numerous recycled ones, which are very robust to degradation. and that they hardly suffer leaching of palladium. An exhaustive evaluation of the catalytic capacities of the PMCs of the present invention focused, but not limited to model reactions of 15 Heck-Mizoroki and Suzuki-Miyaura with aryl halides, with which their kinetic profiles have been analyzed ( % conversion vs. time), its recyclability in successive catalysis-recovery-reuse tests, the maintenance of its properties in the recycling series and the leachate suffered by the PMCs in the mines. Below is a selection of results, the procedures used are described in examples 20 of this invention and the evaluation of the catalytic properties consists in: I) testing the PMCs of this invention in Suzuki-Miyaura reactions between an arylboronic acid, preferably phenylboronic acid, with aryl halides, preferably 4-bromo- and 4-chlorotoluene, at a mild temperature (65-80 ° C), in a mechanically stirred aqueous organic medium at constant speed in the presence of small amounts of surfactants non-ionic with high hydrophilic-hydrophobic balance (HLB> 15, used below its critical level of concentration) and with low loads of 16
palladium (0.024-0.050 mol% [Pd], with respect to the corresponding haloarene used as the limiting substrate). Table 3 collects the results obtained with especially preferred PMCs. Table 3 Results in the Suzuki-Miyaura reaction with the PMCs in the examples. substrate precursor input medium D T (° C) t (h) conversion (%) to ld PMC (Yes) I1 PMC (Yes) I2 PMC (Si) I2 PMC (S1) 13 PMC (Yes) 12 PMC (Yes) I3 4 -bromotoluene 4-bromotoluene 4-bromotoluene 4-bromotoluene 4-chlorotoluene 4-chlorotoluene Tx / Et0H Tx / Et0H Tx / THF Tx / Et0H Tx / Et0H Tx / Et0H 65 65 65 65 80 80 2 2 2 2 5 5 70 92 50 85 80 76 PMC (Si) I11 4-bromotoluene Tx / THF 65 15 86 PMC (S1) 112 4-bromotoluene Tx / THF 65 15 100 PMC (Si) I13 4-bromotoluene Tx / THF 65 15 100 2e'f PMC ( S1) 111 4-chlorotoluene Tx / THF 80 30 51 PMC (S1) 112 4-chlorotoluene Tx / THF 80 30 77 PMC (S1) 113 4-chlorotoluene Tx / THF 80 30 68 PMC (A) I11 4-bromotoluene Tx / THF 65 15 91 PMC (A) II2 4-bromotoluene Tx / THF 65 15 100 3e, f PMC (A) II3 4-bromotoluene TilTHF 65 15 100 PMC (S1) 111 4-chlorotoluene Tx / THF 80 30 56 PMC (A ) II2 4-chlorotoluene Tx / THF 80 30 82 PMC (A) II3 4-chlorotoluene Tx / THF 80 30 72 PMC (A) III4 4-bromotoluene Tx / THF 65 20 100 4e'f PMC (A) III4 4-chlorotoluene Tx / THF 80 48 100 Against phenylboronic acid. Tx / Et0H (1: 4), Tx / THF (9: 1). Tx = solution of Trit & in "X405 in water to Determined by gas chromatography with FID detector. Reproducibility ± 3%. Metal load: 0.05 mol% [Pd]. e Metal load: 0.024 mol% [Pd]. f Total conversion at 30 h with 4-bromotoluene with PMC (S1) 111 and PMC (A) 111, at 82 h with 4-chlorotoluene with PMC (Si) 112 y3 and PMC (A) I13 and 3, and at 90 hours with the PMC (Si) 111 and PMC (A) II. 5 m) test the PMCs of this invention in Heck-Mizoroki reactions between an olefin, preferably an acrylate with aryl halides, preferably 4- iodotoluene, at a mild temperature (5 90 ° C), in a stirred organic-aqueous medium mechanically at constant speed () in the presence of small amounts of 10 non-ionic surfactants with high hydrophilic-hydrophobic balance (HLB> 15, used by 17
below its critical micellar concentration) and with low palladium loads (0.024-0.050 mol% [Pd], with respect to the haloarene used as the limiting substrate). Table 4 shows the results obtained with the especially preferred PMCs. Table 4 Results in the Heck-Mizoroki reaction with the PMCs in the examples. substrate precursor input medium D T (° C) t (h) Conversion (%) to PMC (S1) 11 4-iodotoluene Tx / THF 90 8 100 1d PMC (Si) I2 4-iodotoluene Tx / THF 90 6 100 PMC (Si ) I3 4-iodotoluene Tx / THF 90 7 100 PMC (Si) 111 4-iodotoluene Tx / THF 90 20 100 2e PMC (Si) 112 4-iodotoluene Tx / THE 90 12 100 PMC (Si) 113 4-iodotoluene Tx / THF 90 15 100 PMC (A) II1 4-iodotoluene Tx / THF 90 20 100 3e PMC (A) II2 4-iodotoluene Tx / THF 90 10 100 PMC (A) II3 4-iodotoluene TX / THE 90 15 100 4e PMC ( A) III4 4-iodotoluene Tx / THF 90 15 100 a Against methyl acrylate. Tx / THF (9: 1). Tx = solution of TritOnTM X405 in water Determined by gas chromatography with FID detector. Reproducibility ± 3%. d Metal load: 0.05 mol% [Pd]. ° Metallic carp: 0.024 mol% [Pd]. 5 n) evaluate the recyclability of the PMCs of this invention, by means of the separation-washing-reuse sequence, in the Suzuki-Miyaura reactions that have been defined previously in the activity tests l), comparing the kinetic profiles of the successive reactions of each series of recycled. Specifically, there have been twelve successive recycling of each catalyst (13 uses counting the initial reaction or recycling numbered 0) by separating the PMCs using an external magnet and decanting the solutions. A selection of graphic representations of some profiles for some of the especially preferred PMCs is as follows: 15 Profile of the initial Suzuki-Miyaura reaction (0) and of the first (1), second (2) recycled ones and twelfth (12) for PMC (S1) 112 with: a) 4-bromotoluene and b) 4- chlorotoluene: 18
80 c 60: or> 40 20 (0) (1) (2) (12) 3 6 15 0 5 10 15 20 25 Reaction time (h) 30 Initial Suzuki-Miyaura reaction profile (0) and of recycled first (1), second (2) and twelfth (12) for PMC (A) II3 with: a) 4-bromotoluene and b) 4- 5 chlorotoluene: 3 6 9 12 15 Reaction time (h) b) 100 . 0 5 10 15 20 25 Reaction time (h) 30 Reaction profile of initial Suzuki-Miyaura (0) and recycled first (1), second (2) and twelfth (12) for PMC (A) III4 with : a) 4-bromotoluene and b) 4- 10 chlorotoluene: a) loo 80 60 40 20 5 10 15 20 Reaction time (h) 19 b) loo 80 C 60 1. 0 8 16 24 Reaction time (h) 32 40 48
o) evaluate the recyclability of the PMCs of this invention, by means of the separation-washes-reuse sequence, in the Heck-Mizoroki reactions that have been previously defined in the activity tests m), comparing the kinetic profiles of the successive reactions of each series of recycled. Specifically, there have been twelve successive recycles of each catalyst (13 uses counting the initial reaction or recycling numbered 0) separating the PMCs using an external magnet and decanting the solutions. A selection of graphical representations of some profiles for some of the especially preferred PMCs, is the one shown below: 15 Profile of the initial Heck-Mizoroki reaction (0) and the recycled first (1), second (2) ) and twelfth (12) with 4-iodotoluene for: a) PMC (S1) 13 and b) PMC (S1) 112: 1 2 3 4 5 6 7 Reaction time (h) 2 4 6 8 10 Reaction time (h ) 12 Profile of the initial Heck-Mizoroki reaction (0) and recycled first (1), second (2) and twelfth (12) PMC (A) II14: a) 100 (2) 80 with 4-iodotoluene for : a) PMC (A) II3 and b) 5 10 Reacciem time (h). 5 20 5 10 Reaction time (h) 15
p) quantify the possible leaching of palladium from the PMCs of this invention, by quantitative elementary analysis of palladium (ICP-MS), both of the separate solutions in each consecutive use and of the PMCs at the end of each series of 5 recycled in the Suzuki-Miyaura reactions that have been previously defined in the activity tests l), correlating the eventual leachate of the PMCs with the slight decreases in the conversions (measured in each case always at the same time) in the successive reactions in each series of the trials defined above in the evaluation n). Table 5 shows an illustrative selection 10 of these correlations in this type of coupling for some of the especially preferred PMCs. Table 5. Conversion drop and leaching of palladium in the recycled, and total% of the metal found in the solutions and lost by the PMCs in Suzuki-Miyaura reactions. recycled precursor N °: 0-1 1. 2 2-3 3-11 12 total lost by the PMCe decrease in PMC (Si) 112` conver. in% at 0 I) 0 9 2 11% Pd leachateb 1.2 0.0 0.2 7.2 0.4 9 n. d. PMC descent (Si) 112d conver. in% at 5 0 0 11 1 17% Pd leachateb 3.8 0.5 0.3 13.0 0.4 18 19 decrease in PMC (A) I13c conver. in ° / 08 0 0 0 7 3 10% Pd leachateb 0.0 0.0 0.0 6.4 2.6 9 8 decrease in PMC (A) I13d conver. in% at 3 0 0 8 2 13% Pd leachateb 4.6 0 0 6.8 2.6 14 n. d. decrease in PMC (A) II14c conver. in% at 0 0 0 0 0 0% Pd leachateb 0.0 0.0 0.0 0.2 0.0 0.2 n. d. decrease in PMC (A) II14d conver. in% at 0 0 0 4 5 9% Pd leachateb 0.1 0.1 0.0 0.5 0.2 0.9 1.5 a Determined by gas chromatography with FID deletor. Reproduability ± 3%. b Determined by Relative Standard Deviations in quantifications 5 10%. With 4-bromotoluene; measured at 15 h for PMC (Si) 112 and PMC (A) II3, and at 20 h for PMC (A) II14. twenty-one
° With 4-chlorotoluene; measured at 30 h for PMC (S1) 112 and PMC (A) II3, and at 48 h for PMC (A) II14. e Measured by ICP-MS on the PMCs themselves after thirteen uses; n. d. = Not determined. q) quantify the possible leaching of palladium from the PMCs of this invention, by quantitative elementary analysis of palladium (ICP-MS), both of the separate solutions in each consecutive use and of the PMCs at the end of each series of 5 recycled in the reactions of Heck-Mizoroky that have been previously defined in the activity tests m), correlating the eventual leachate of the PMCs with the slight decreases in the conversions (measured in each case always at the same time) in the successive reactions in each series of the tests that have been previously defined in the evaluation o). Table 6 shows an illustrative selection 10 of these correlations in this type of coupling for some of the especially preferred PMCs. Table 6. Reduction of conversion and leaching of palladium in the recycled, and total% of the metal found in the solutions and lost by the PMCs in Heck-Mizoroky reactions. a Determined lost by recycled precursor N °: 0-1 1-2 2-3 3-11 12 total PMCs d decrease in PMC (Si) 13b conver. in% at 0 0 0 9 2 11% Pd leachate 1.9 0.9 0.9 8.0 1.3 13 n. d. PMC descent (Si) 112c conver. in% at 0 0 0 8 1 9% Pd leachateb 0.8 0.0 0.2 6.9 1.1 9 11 decrease in PMC (A) I13c conver. in% at 0 0 0 4 1 5% Pd leachateb 0.5 0.3 0.1 3.1 1.0 5 7 decrease in PMC (A) 1114` conver. in% at 0 0 0 0 0 0% Pd leachateb 0.0 0.0 0.0 0.02 0.0 0.02 0.18 pair gas chromatography with FID detector. Reproducibility ± 3%. b Determined by ICP-MS. Standard Relative Deviations in quantifications s 10%. Measures at 7 o'clock for PMC (Si) I3, at 12 o'clock stop PMC (Si) 112 and at 15 o'clock for PMC (A) II3 and PMC (A) II14. d Measured by ICP-MS on the PMCs themselves after thirteen uses; n. d. = Not determined °. r) determine the productivity (TON ° or "turnover number" in the first use of the catalyst) and activity (TOF0 or "turnover frequency" in the first use of the 22
catalyst) of the PMCs of this invention in the initial Suzuki-Miyaura reactions that have been previously defined in the activity tests I), as well as the accumulated TON (TONT) and the average TOF (TOFAv) in each series of consecutive uses which have been described previously in the evaluation n), together with the palladium content found in the products whose determination is described in the quantifications p). Table 7 and Table 8 collect the values found in the Suzuki-Miyaura reactions for some of the especially preferred PMCs of this invention. 10 Table 7. TOF and TON values shown for some PMCs of the examples in the Suzuki-Miyaura reaction with 4-bromotoluene and the metal content found in the products. TON TOFAv TON— TOFA ,, Precursor content TONob TONTG (hl) b 01-1) c (11-1) Pd (ppm) d PMC (Si) 111 3584 239 42128 216 23 3 PMC (Yes) 112 4167 278 52046 267 11 1 PMC (Yes) 113 4167 278 52088 267 11 2 PMC (A) II1 3792 253 43624 224 29 3 PMC (A) 1I2 4167 278 53046 272 6 1 PMC (A) 113 4167 278 52629 270 9 1 PMC (A) 1114 4167 208 53879 207 1 0.023 a Reaction times: 20 h for PMC (A) III4, 15 h for the rest Value in the initial reaction. Value in the thirteen uses of the catalyst. d Palladium contamination of the product in parts per milk: 0 by mass. Table 8 TOF and TON values shown for some PMCs of the examples in the Suzuki-Miyaura reaction with 4-chlorotoluene and the metal content found in the products. TON TOFAv TON - TOFA, Precursor content TONob TONT` (11-1) b (h-1) `(h-1) Pd (ppm) d PMC (Si) I11 2125 71 22085 57 14 10 PMC (Yes) 112 3209 107 3650: 3 94 13 3 PMC (S1) 113 2834 94 32128 82 12 3 PMC (A) II1 2334 78 25210 65 13 7 PMC (A) I12 3417 114 39211 101 13 2 PMC (A) I13 3042 101 36545 94 7 2 PMC (A) 1114 4167 87 53254 85 2 0.107 23
a Reaction times: 48 h for PMC (A) III4, 30 h for the rest b Value in the initial reaction. Value in the thirteen uses of the catalyst. d Contamination by product palladium in parts per million in mass. s) determine the productivity (TON () or "turnover number" in the first use of the catalyst) and activity (TOF0 or 'turnover frequency "in the first use of the catalyst) values of the PMCs of this invention in the initial reactions of Heck-5 Mizoroki that have been previously defined in the m) activity tests, as well as the accumulated TON (TONT) and the average TOF (TOFA,) in each series of consecutive uses that have been previously described in the evaluation), together with the palladium content found in the products whose determination is described in the quantifications q). Table 9 collects the values found in Heck-Mizoroki reactions 10 for the PMCs of the examples of this invention. Table 9 TOF and TON values shown by the PMCs of the examples in the Heck-Mizoroki reaction with 4-iodotoluene and the metal content found in the products. precursor TONob TON (11-1) b TONT` TOFAv (h-1) `TOF0 - TOFA, (11-1) Pd content (ppm) d PMC (S1) 11 2000 250 24400 235 15 5 PMC (Yes) I2 2000 333 25 100 322 11 4 PMC (S1) 13 2000 286 25260 278 8 3 PMC (Yes) II1 4167 208 52421 202 6 2 PMC (Yes) 112 4167 347 52963 340 7 1 PMC (Yes) 113 4167 278 53254 273 5 1 PMC (A) II1 4167 208 52921 204 4 2 PMC (A) 112 4167 417 53463 411 6 1 PMC (A) 1I3 4167 278 53504 274 4 1 PMC (A) 1I14 4167 278 53963 277 1 0.002 Reaction times: 8 (PMC (Yes) 11), 6 (PMC (Si) 12), 7 (PMC (Si) 13), 20 (PMC (S0111 and PMC (A) II1), 12 (PMC (Si) I12), 10 (PMC ( A) I12) and 15 h (PMC (Si) I13, PMC (A) II3 and PMC (A) II14. b Value in the initial reaction. Value in the thirteen uses of the catalyst. d Contamination by product palladium in parts per million. t) additionally and finally, analyze the TEM (Electron Microscopy of 15 Transmission) images of the PMCs, both before their use in the reactions that have occurred.
defined above in the activity tests I) and m) as at the end of the series of recycles that have been previously defined in the evaluations n) i), as well as samples prepared from the separate solutions in each reaction, verifying that the PMCs they do not undergo appreciable morphological changes and that no aggregates of metallic palladium are observed next to them or in the samples prepared from the solutions separated with the products at the end of each reaction. 10 15 DESCRIPTION OF THE DRAWINGS Figure 1. Schematic representation of the heterogeneization of the CPs to give the PMCs object of the present invention. Figure 2 Schematic representation of the CPs object of the present invention. Figure 3 Synthesis scheme of the new CPs of types I, II and III and their precursors. Figure 4 Profile of the initial Suzuki-Miyaura (0) and recycled first 20 (1), second (2) and twelfth (12) for PMC (S1) 112 with: a) 4-bromotoluene and b) 4-chlorotoluene. Figure 5 Profile of the initial Suzuki-Miyaura reaction (0) and the first (1), second (2) and twelfth (12) recycled ones for PMC (A) II3 with: a) 4-bromotoluene and b) 25 4-chlorotoluene. 30 Figure 6. Profile of the initial Suzuki-Miyaura reaction (0) and the first (1), second (2) and twelfth (12) recycled ones for PMC (A) III4 with: a) 4-bromotoluene and b) 4-chlorotoluene. Figure 7 Profile of the initial Heck-Mizoroki (0) and recycled first (1), second (2) and twelfth (12) reactions with 4-iodotoluene for: a) PMC (S1) 13 and b) PMC (S1) 112 . 35 Figure 8. Profile of the initial Heck-Mizoroki (0) and recycled first (1), second (2) and twelfth (12) reactions with 4-iodotoluene for: a) PMC (A) II3 and b) 25
PMC (A) II14. MODE OF EMBODIMENT OF THE INVENTION 5 The present invention is further illustrated by the following illustrative examples, although not limiting, in which experimental procedures, spectroscopic and analytical data of palladium complexes and their precursors and magnetic particles with the complexes are indicated. supported, as well as catalytic tests with them. Example 1. Preparation of the imidazolium salt 1. one. In a 100 mL ampoule, equipped with a tefle punzem valve, n, N-15 methylimidazole (0.65 g, 7.8 mmol) and N- (2-Bromoethyl) phthalimide (1.00 g, 3.9 mmol), in about 40 mL of THF and heated with stirring to 80 ° C. After 16 h, the presence of a white precipitate was observed which, after filtering, was washed) with hexane (2 x 10 mL) to remove excess N-methylimidazole and dried) under vacuum. Product 1 was obtained. 1 as a white solid (1.18 g, 90%). Anal. Calc. for C14H1402N3Br. H20 (354.20): C, 47.47; H, 4.55; N, 20 11.86%. Found: C, 47.42; H, 4.24; N, 11.93%. 1H NMR (CDCI3, 300 MHz): ô4.06 (s, 3H, Imz-Me), 4.23 (t, 3. 4th = 5.4 Hz, 2H, CH2ftal), 4.79 (t, 34, H = 5.4 Hz, 2H, CH2Innz), 7.25 and 7.26 (2 xs, 2 x 1H, Imz-H4y H5), 7.73 (m, 2H, o-ftal), 7.80 (m, 2H, m-ftal), 10.57 (s, 1H, Imz-H2). 13C NMR {1H} (CDCI3, 75 MHz): 6 35.3 (CH2ftal), 37.5 (lmz-Me), 47.4 (CH2Imz), 122.4 and 123.1 (Imz-C4 and C5) , 122.7 (o-ftal), 131.0 (ipso-ftal), 134.1 (m-ftal), 136.6 (Imz-C2), 167.27.2 (C = 0). MS (ESI + / TOF, CH2C12 / Me0H / 5mM NH4HCOO): m / z 256.1092 [M-Br]. 30 1. 1 Example 2. Preparation of the imidazolium salt 1. 2. Compound 1. 2 be prepared) similar to that described for salt 1. 1 of Example 1, starting with N-mesitylimidazole (0.50 g, 2.7 mmol) and N- (2-bromoethyl) phthalimide (0.34 g, 1.4 26
mmol), in THF (40 mL), at 90 ° C and for 16 h. Compound 1 was obtained. 2 eat a white oiled solid (0.56 g, 95%). Anal. Calc. for C22H2202N3Br (440.34): C, 60.01; H, 5.04; N, 9.54%. Found: C, 59.75; H, 5.06; N, 9.47%. 1H NMR (CDCI3, 300 MHz): 6 2.09 (s, 6H, Month-o-Me), 2.31 (s, 3H, Month-p-Me), 4.33 (t, JH, H = 5.0 Hz, 2H, 5 CH2ftal), 5.14 (t, 34, H = 5.0 Hz, 2H, CH2Imz), 6.97 (s, 2H, m-Month), 7.04 and 7, 51 (2 xt, = 1.9 Hz, 2 x 1H, Imz-H4 and H5), 7.73 (m, 2H, o-ftal), 7.78 (m, 2H, m-ftal), 10, 50 (t, 3JH, H = 1.9 Hz, 1H, Imz-H2). 13C NMR {1H} (CDCI3, 75 MHz): 617.6 (Month-p-Me), 21.1 (Month-o-Me), 39.0 (CH2ftal), 49.6 (CH2Imz), 122, 8 and 123.0 (Imz-C4 and C5), 123.7 (o-ftal), 129.9 (m-Month), 130.6 (ipso-Month), 131.5 (ipso-ftal), 134 , 4 (o-Month), 134.5 (m-ftal), 138.8 (Imz-C2), 141.4 (p-10 Month), 167.2 (C = 0). MS (ESI + / TOF, CH2C12 / Me0H / 5mM NR4HCOO): m / z 360.1711 [M-Br]. one. 2 15 Example 3. Preparation of the imidazolium salt 1. 3. Compound 1. 3 was prepared similarly to that described for salt 1. 1 of Example 1, starting with N- (2,6-diisopropylphenyl) imidazole (0.50 g, 2.2 mmol) and N- (2-bromoethyl) phthalimide (0.28 g, 1.1 mmol), in THF (40 mL), at 90 ° C and for 16 h. Compound 1 was obtained. 3 20 as an oily white solid (0.48 g, 90%). Anal. Cale. for C25H2802N3Br. 1.2H20 (505.04): C, 59.57; H, 6.08; N, 8.34%. Found: C, 59.96; H, 5.95; N, 7.92%. 1H NMR (CDCI3, 300 MHz): 61.11 (d, 34, H = 7.0 Hz, 6H, CH (CH3) 2), 1.23 (d, JH, H = 7.0 Hz, 6H, CH (CH3) 2), 1.83 (Sep, 3JH, H = 7.0 Hz, 2H, CH (CH3) 2), 4.35 (t, 3JH, H = 5.2 Hz, 2H, CH2ftal) , 5.22 (t, 3JKH = 5.2 Hz, 2H, CH2Imz), 7.03 and 7.58 (2 xs, 2 x 1H, Imz-H4 and H5), 7.04 (d, 25 = 7 , 9 Hz, 2H, m-Ph), 7.51 (t, JH, H = 7.9 Hz, 1H, p-Ph), 7.73 (m, 2H, o-ftal), 7.80 ( m, 2H, m-ftal), 10.51 (broad s, 1H, Imz-H2). 13C NMR {1H} (CDCI3, 75 MHz): 6 24.3 (CH (CH3) 2), 24.5 (CH (CH3) 2), 28.5 (CH (CH3) 2), 39.2 ( CH2ftal), 49.7 (CH2Imz), 123.0 and 123.8 (Imz-C4 and C5), 123.6 (m-Ph), 124.7 (o-ftal), 130.1 (ipso-Ph ), 131.6 (ipso-ftal), 131.9 (o-Ph), 134.5 (m-ftal), 138.9 (Imz-C2), 145.5 (p-Ph), 167.7 (C = 0). MS (ESI + / TOF, CH2C12 / Me0H / 5 mM NH4HCOO 30): miz 402.2176 [M-Br]. 27
0 1c Example 4. Preparation of the imidazolium salt 2 (51) 1. In a 50 mL ampoule with (3-bromopropyl) triethoxysilane (0.29 g, 1.0 mmol), it was emptied for 10 min and 2 mL of dry CH3CN was added. Then N-methylimidazole (0.08 g, 1.0 mmol) was added. The resulting yellow solution was left under stirring at 100 ° C for 16 h, then evaporated the solvent. The resulting yellow oil was washed with hexane (2 x 15 mL), obtaining compound 2 (51) 1 as a yellow oil (0.33 g, 89%). Anal. Calc. for C13H2703N2SiBr (367.36): C, 42.50; H, 7.41; N, 7.62%. Found: C, 42.00; H, 6.85; N, 8.04%. 1H NMR (CDCI3, 300 MHz): 6 0.52 (t, = 8.5 Hz, 2H, SiCH2), 1.12 (t, 3s / H, H = 7.0 Hz, 9H, CH3CH20), 1 , 93 (m, 2H, SiCH2CH2), 3.72 (c, 3JH, H = 7.0 Hz, 6H, CH3CH20), 4.04 (s, 3H, lmz-Me), 4.24 (t, 3AH = 7.2 Hz, 2H, CH2Imz), 7.31 and 7.57 (2 xt, 341, H = 1.6 Hz, 2 x 1H, Imz-H4 and H5), 10.2 (s, 1H, Imz-H2). 13 C NMR {1H} (CDCI3, 75 MHz): 6 7.0 (SiCH2), 18.2 (CH3CH20), 24.3 (S1CH2CH2), 36.6 (lmz-Me), 51.6 (CH2Imz) , 58.5 (CH3CH20), 121.7 and 123.5 (Imz-C4 and C5), 137.4 (Imz-C2). MS (ESIF / TOF, CH2C12 / Me0H / 5 mM NH4HCOO): tniz 247.1780 [M-Br]. 20 Br-2 (Yes) 1 Example 5. Preparation of the imidazolium salt 2 (Si) 2. Compound 2 (51) 2 was prepared in a manner similar to that described for salt 2 (51) 1 of Example 4, starting with N-mesitylimidazole (0.22 g, 1.2 mnnol) and the brominated derivative (0, 34 25 g, 1.2 mmol), in CH3CN (2.5 mL), at 100 ° C and for 24 h. All solid reagents were previously held in vacuo for 10 min. Compound 2 (51) 2 was obtained as an oiled white solid (0.55 g, 98%). Anal. Calc. for C211-13503N2SiBr. 0.1H20 (489,530): C, 53.29; H, 7.50; N, 5.92%. Found: C, 52.77; H, 7.12; N, 6.46%. 1H NMR (CDCI3, 300 MHz): 60.62 (m, 2H, SiCH2), 1.18 (t, 3 JitH = 7.0 Hz, 9H, CH3CH20), 2.04 (s, 28
6H, Month-o-Me), 2.07 (m, 2H, SiCH2CH2), 2.30 (s, 3H, Month-p-Me), 3.80 (c, 3JH, H = 7.0 Hz, 6H, CH3CH20), 4.72 (t, 3JH, H = 7.0 Hz, 2H, CH2Imz), 6.96 (s, 2H, m-Month), 7.15 and 7.67 (2 xt, 34 , H = 1.5 Hz, 2 x 1H, Imz-H4 and H5), 10.4 (wide s, 1H, Imz-H2). 13C NMR {1H} (CDCI3, 75 MHz): 6 6.8 (SiCH2), 17.6 (Month-o-Me), 18.2 (CH3CH20), 21.0 (Month-p-Me), 24 , 5 5 (S1CH2CH2), 52.0 (CH2Imz), 58.6 (CH3CH20), 122.7 and 122.9 (Imz-C4y C5), 129.8 (m-Month), 130.6 (ipso- Month), 134.1 (o-Month), 138.2 (Imz-C4), 141.2 (p-Month). MS (ESI + / TOF, CH2C12 / Me0H / 5mM NH4HCOO): m / z 391.2412 [M-Br]. 10 (Et0) 3 Yes. ,, N • It • N Br-2 (Yes) 2 Example 6. Preparation of the imidazolium salt 2 (Si) 3. Compound 2 (S1) 3 was prepared similarly to that described for salt 2 (Si) 1 of Example 4, starting from N- (2,6-diisopropylphenyl) imidazole (0.28 g, 1.2 mmol) and the brominated derivative (0.34 g, 1.2 mmol), in CH3CN (2.5 mL), at 100 ° C and for 24 h. All solid reagents were emptied for 10 min before use. Compound 2 (Si) 3 was obtained as a white solid of oily appearance (0.61 g, 99%). Anal. Calc. for C24H4103N2SiBr- (2.4CH3CN and 2C3H60) (728.28): C, 57.52; H, 8.03; N, 7.62%. Found: C, 57.91; H, 8.03; N, 7.27%. 1H NMR (CDCI3, 300 MHz): ô0.61 (t, 3JKH = 7.7 20 Hz, 2H, S1CH2), 1.13 (d, 3JH, H = 7.2 Hz, 6H, CH (CH3) 2 ), 1.18 (t, 3JH, H = 7.0 Hz, 9H, CH3CH20), 1.20 (d, 34, H = 7.2 Hz, 6H, CH (CH3) 2), 2.07 ( m, 3JH, H = 7.7 Hz, 2H SiCH2CH2), 2.25 (Sep, 3JH, H = 7.2 Hz, 6H, CH (CH3) 2), 3.78 (c, 3JH, H = 7 , 0 Hz, 6H, CH3CH20), 4.78 (t, 3.41, H = 7.7 Hz, 2H, CH2Imz), 7.18 and 7.88 (2 xs wide, 2 x 1H, Imz-H4 and H5), 7.27 (d, 2H, 34H = 7.6 Hz, m-Ph), 7.49 (t, 1H, 3JH, H = 7.6 Hz, p-Ph), 10.3 ( s, 1H, Imz-H2). 13C NMR {1H} 25 (CDCI3, 75 MHz): 6 6.6 (SiCH2), 18.2 (CH3CH20), 24.0 (CH (CH3) 2), 24.3 (CH (CH3) 2), 24.5 (S1CH2CH2), 28.6 (CH (CH3) 2), 52.0 (CH2Imz), 58.5 (CH3CH20), 123.0 and 124.0 (Imz-C4 and C5), 124.6 (m-Ph), 130.0 (ipso-Ph), 131.8 (C6H3 (o-Ph), 138.2 (Imz-C2), 145.2 (p-Ph). MS (ESI + / TOF, CH2C12 / Me0H / 5mM NH4HCOO): miz 433.2881 [M-29
2 (Yes) 3 Example 7. Preparation of the imidazolium salt 2 (A) 1. 5) Hydrazine (2.10 mL, 43.1 mmol) is added to a 50 mL vial with imidazolium 1 salt. 1 described in Example 1 (1.40 g, 4.3 mmol) in 25 mL of 2-propanol and heated at 40 ° C overnight. The initial white suspension is taken) at a clear solution with the progress of the reaction to finally precipitate a white solid that corresponds to the by-product of the deprotection, phthalylhydrazine. The mixture was cooled, filtered and evaporated to obtain the desired product 2 (A) 1 as a yellow oil (0.80 g, 95%). Anal. Calc. for C6H12N2Br (206.08): C, 34.97; H, 5.87; N, 20.39%; Found: C, 34.31; H, 5.98; N, 19.89%. 1H NMR (CDCI3, 300 MHz): ö 3.19 (t, 3J11, H = 5.6 Hz, 2H, NH2CH2), 4.05 (s, 3H, lmz-Me), 4.44 (t, 3 , 40. 1 = 5.6 Hz, 2H, CH2Imz), 7.27 and 7.49 (2 x s, 2 x 1H, Imz-H4 and H5), 10.33 (s, 1H, Imz-H2). 13C NMR {1H} (CDCI3, 75 MHz): 6 15 36.7 (NH2CH2), 41.4 (lmz-Me), 52.3 (CH2Imz), 122.3 and 122.5 (Imz-C4 and C5 ), 138.6 (Imz-C2). MS (ESI + / TOF, CH2C12 / Me0H / 5mM NH4HCOO): miz 126,1026 [M-Br]. m Br-2 (A) 1 20 Example 8. Preparation of the imidazolium salt 2 (A) 2. Compound 2 (A) 2 is prepared) in a manner similar to that described for salt 2 (A) 1 of Example 7, starting from imidazolium salt 1. 2 described in Example 2 (1.29 g, 2.9 mmol) and hydrazine (1.43 mL, 29.0 mmol), in isopropanol, at 40 ° C and overnight. After filtering, evaporating and washing with hexane, the imidazolium salt 2 (A) 2 was obtained as a yellow oil (0.87 g, 95%). Anal. Calc. for C14H20N3Br. 0.7H20 (322.84): C, 52.08; H, 6.68; N, 13.02%; Found: C, 51.82; H, 6.34; N, 13.24%. 1H NMR (CDCI3, 300 MHz): 6 2.05 (s, 6H, Month-o-Me), 2.31 (s, 3H, Month-p-Me), 3.23 (t, 3JH, H = 5.6 Hz, 2H, NH2CH2), 4.81 (t, 3JKH = 5.6 Hz, 2H, CH2Imz), 6.97 (s, 2H, in-Month), 7.11 and 7.91 (2 xt, 3JH, H = 1.7 Hz, 2 x 30
5 1H, Imz-H4 and H5), 10.09 (t, 34, H = 1.7 Hz, 1H, Imz-H2). 13C NMR {1H} (CDCI3, 75 MHz): 6 17.8 (Month-p-Me), 21.0 (Month-o-Me), 40.9 (NH2CH2), 50.3 (CH2Imz), 123 , 0 and 124.0 (Imz-C4 and C5), 129.7 (m-Month), 130.7 (ipso-Month), 134.4 (o-Month), 137.9 (Imz-C2), 141.0 (p-Month). MS (ESI + / TOF, CH2C12 / Me0H / 5mM NH4FICOO): m / z 230.1652 [M-H2NZ2N Br 2 (A) 2 Example 9. Preparation of the imidazolium salt 2 (A) 3. Compound 2 (A) 3 was prepared similarly to that described for salt 2 (A) 1 of Example 7, starting from imidazolium salt 1. 3 described in Example 3 (0.46 mL, 9.50 mmol) and hydrazine (0.46 mL, 9.50 mmol), in isopropanol, at 40 ° C and overnight. After filtering, evaporating and washing with hexane, the imidazolium 2 (A) 2 salt was obtained as a yellow oil (0.31 g, 92%). Anal. Calc. for C17H26N3Br-0.4H20: C, 56.79; H, 7.51; N, 11.69%; Found: C, 57.07; H, 7.98; N, 12.13%. 1H NMR (CDCI3, 300 MHz): (51.17 (d, 3JKH = 6.9 Hz, 12H, CH (CH3) 2), 2.31 (Sep. , 34H = 6.9 Hz, 2H, CH (CH3) 2), 3.22 (t, 34H = 5.4 Hz, 2H, NH2CH2), 4.87 (t, 34tH = 5.4 Hz, 2H, CH2Imz), 7.12 and 7.58 (2 xt, 3.41, H = 1.3 Hz, 2 x 1H, Imz-H4 and H5), 7.28 (d, 3. 41, H = 7.9 Hz, 2H, m-Ph), 7.52 (t, 3JKH = 7.9 Hz, 1H, p-Ph), 10.51 (t, 3JKH = 1.3 Hz, 1H , Imz-H2). 13C NMR {1H} (CDCI3, 75 MHz): (5 24.1 20 (CH (CH3) 2), 24.4 (CH (CH3) 2), 28.6 (CH (CH3) 2), 41, 6 (NH2CH2), 51.6 (CH2Imz), 123.2 and 123.5 (Imz-C4 and C5), 124.7 (m-Ph), 130.1 (ipso-Ph), 131.9 (or -Ph), 139.0 (Imz-C2), 145.5 (p-Ph). MS (ESIIITOF, CH2C12 / Me0H / 5 mM NH4HCOO): m / z 272,2082 [M-Br]. 25 2 (A) 3 Example 10. Preparation of the palladium complex l (Si) 1. The imidazolium 2 (Si) 1 salt described in Example 4 (0.58 g, 1.6 mmol), palladium chloride (0.28 g, 1.6 mmol), carbonate carbonate were weighed under an argon under argon. potassium (1.09 g, 31
7.9 mmol) and sodium iodide (1.66 g, 11.1 mmol), and placed in a Buchi desiccator at 10 mbar and 95 ° C for 24 h. Subsequently, 12 mL of 4-picoline was added, previously treated with shieve molecules overnight, forming a reddish suspension that was allowed to stir at 80 ° C for 24 hours under argon. After evaporating the 4-picoline, 5 was extracted with CHCI3, the solution was filtered and hexane was added to remove palladium halide residues. After filtering and evaporating the solvent, complex 1 (Si) I was obtained as a yellow powdery solid (1.12 g, 96%). Anal. Calc. for C19H3303N312S1Pd (739.80): C, 30.85; H, 4.50; N, 5.68%. Found: C, 30.36; H, 4.40; N, 5.93%. 1H NMR (CDCI3, 300 MHz): 6 0.73 (t, 3JH, H = 8.0 Hz, 2H, S1CH2), 1.21 (t, 34H = 7.0 Hz, 9H, 10 CH3CH20), 2 , 15 (m, 2H, SiCH2CH2), 2.35 (s, 3H, plc-Me), 3.83 (c, 34, H = 7.0 Hz, 6H, CH3CH20), 3.95 (s, 3H , lmz-Me), 4.38 (t, 34, H = 8.0 Hz, 2H, CH2Imz), 6.90 and 6.96 (2 xd, 3.41.11 = 2.0 Hz, 2 x 1H, Imz-H4 and H5), 7.09 (d, 3JH, H = 5.9 Hz, 1H, m-pic), 8.83 (d, 34, H = 5.9 Hz, 1H, or- pic). 13C NMR {1H} (CDCI3, 75 MHz): 67.7 (SiCH2), 18.4 (CH3CH20), 21.1 (pic-Me), 23.1 (SiCH2CH2), 39.2 (lmz-Me) , 537 (CH2Imz), 58.6 (CH3CH20), 121.7 and 123.0 15 (Imz-C4 and C5), 125.3 (m-pic), 145.6 (Imz-C2), 149.4 (p-pic), 153.2 (o-pic). IR (KBr): v 3050-3120 (m, Csp-H st), 1618 (m, C = C st), 1542 (s, C = N st), 1420-1470 (m, arC = C st), 1080 (w, Si-OC st), 957 (w, Si-OC st), 806 (m, Si-C st), 687 cm-1 (m, Si-0 st). MS (ESI + / TOF, CH2C12 / Me0H / 5mM NH4HCOO): ink 740.9418 [M + H. 20 (Et0) 3SiNN ,, I-Pd-I. ) \ 1 I (Yes) 1 Example 11. Preparation of the palladium complex l (Si) 2. Compound 1 (Si) 2 was prepared as described for complex 1 (S1) 1 of Example 25 10, starting from the imidazolium salt 2 (Si) 2 described in Example 5 (0.57 g, 1, 2 mmol), palladium chloride (0.21 g, 1.2 mmol), potassium carbonate (0.83 g, 6.0 mmol) and sodium iodide (1.26 g, 8.4 mmol), in 12 mL of 4-picoline, at 100 ° C and for 16 h. Compound 1 (Si) 2 was obtained as an orange powdery solid (0.99 g, 98%). Anal. Calc. for C27H4103N3I2SiPd (843.95): C, 38.43; H, 4.90; N, 4.98%. Found: C, 38.22; 30 H, 4.78; N, 5.36%. 1H NMR (CDCI3, 300 MHz): 6 0.80 (t, JH, H = 8.2 Hz, 2H, S1CH2), 1.25 (t, 3JRH = 7.0 Hz, 9H, CH3CH20), 2, 25 (m, 2H, SiCH2CH2), 2.28 (s, 3H, pic-Me), 2.30 (s, 32
6H, Month-o-Me), 2.34 (s, 3H, Month-p-Me), 3.86 (c, 34, F, = 7.0 Hz, 6H, CH3CH20), 4.62 (t , 34, H = 7.0 Hz, 2H, CH2Imz), 6.87 and 7.24 (2 xd, 34, F, = 2.0 Hz, 2 x 1H, Imz-H4 and H5), 6.97 (s, 2H, m-Month), 6.98 (d, 34, H = 5.6 Hz, 2H, m-plc), 8.53 (d, 34, H = 5.6 Hz, 2H, or -pic). 13C NMR {1H} (CDCI3, 75 MHz): 6 7.7 (SiCH2), 18.4 (CH3CH20), 21.0 (Month-p-Me), 21.1 (pic-Me), 5 21, 7 (Month-o-Me), 23.3 (SiCH2CH2), 55.0 (CH2Imz), 58.6 (CH3CH20), 121.3 and 136.1 (lmz-y C5), 125.1 (m- plc), 129.4 (m-Month), 135.0 (ipso-Month), 139.0 (p-Month), 148.4 (o-Month), 149.1 (p-pic), 152, 9 (o-pic). IR (KBr): v 3070-3160 (m, arC-H st), 1618 (m, arC = C st), 1531 (s, C = N st), 1400-1480 (m, arC = C st), 1076 (w, Si-OC st), 956 (w, Si-OC st), 806 (m, Si-C st), 692 cnri-1 (m, Si-0 st). MS (ESIf / TOF, CH2C12 / Me0H / 5mM NH4HCOO): m / z 10 862.0312 [M + NH4], 845.0154 [M + H], 717.0939 [M-Ir. I (Yes) 2 Example 12. Preparation of the palladium complex l (Si) 3. Compound 1 (Si) 3 was prepared similarly to that described for complex 1 (51) 1 of Example 10, starting from the imidazolium salt 2 (Si) 3 described in Example 6 (0.62 g, 1.2 mmol), palladium chloride (0.21 g, 1.2 mmol), potassium carbonate (0.83 g, 6.0 mmol) and sodium iodide (1.28 g, 8.4 mmol) , in 12 mL of 4-picoline, at 100 ° C and for 16 h. Compound 1 (51) 3 was obtained as a powdery & Nick) orange powder (0.99 g, 98%). Anal. Calc. for C30H4703N3I2S1Pd (843.95): C, 40.67; H, 5.35; N, 4.74%. Found: C, 41.03; H, 5.75; N, 5.21%. 1H NMR (CDCI3, 300 MHz): 6 0.82 (d, 34, F, = 7.9 Hz, 2H, SiCH2), 0.99 (d, 3JH, H - = 6.9 Hz, 6H, CH (CH3) 2), 1.24 (t, 34, H = 6.9 Hz, 9H, CH3CH20), 1.38 (d, 34, H = 6.9 Hz, 6H, CH (CH3) 2), 2.23 (m, 2H, S1CH2CH2), 2.27 (s, 3H, plc-Me), 3.10 (h, 25 JH, H = 6.9 Hz, 6H, CH (CH3) 2), 3 , 85 (c, 3JH H = 6.9 Hz, 6H, CH3CH20), 4.68 (t, 34, H - = 7.9 Hz, 2H, CH2Imz), 6.98 (2 xt, 3H, 34, H = 6.6 Hz, 34, H = 2.0 Hz, Imz-H4 and o-pic, overlapping), 7.13 (d, 3JH, H = 2.0 Hz, 1H, Imz-H5), 7 , 28 ((1, 34, H = 7.9 Hz, 2H, m-Ph), 7.46 (t, 34, H = 7.9 Hz, 1H, p-Ph), 8.54 (d, 3JH, F, = 6.6 Hz, 2H, 0-plc). 13C NMR {1H} (CDCI3, 75 MHz): ô 7.7 (S1CH2), 18.4 (CH3CH20), 21.0 (plc-Me), 23.2 (S1CH2CH2), 23.9 (CH (CH3 ) 2), 26.5 30 (CH (CH3) 2), 28.8 (CH (CH3) 2), 55.4 (CH2Irnz), 58.6 (CH3CH20), 120.3 and 130.3 (Imz -C4 and C5), 124.2 (m-Ph), 125.1 (m-plc), 126.7 (p-Ph), 134.7 (ipso-Ph), 147.0 (o-Ph) , 149.1 (p-33
5 foot), 152.8 (o-pic). ). IR (KBr): v 3030-3133 (m, arC-H st), 1619 (m, arC = C st), 1503 (s, C = N st), 1400-1460 (m, arC = C st), 1077 (w, Si-OC st), 957 (w, Si-OC st), 804 (m, Si-C st), 692 cm-1 (m, Si-0 st). MS (ESI + / TOF, CH2C12 / Me0H / 5mM NH4HCOO): rn / z 904.0818 [M + Nftsr, 887.0560 [M + H]. / - = \ (Eto) 3si N and N-ip r2 Ph I-pd-I Example 13. Prepared & Silver Complex 3 (Si) 1. The imidazolium 2 (Si) 1 salt described in Example 4 (1.28 g, 3.5 mmol) and the silver oxide (0.40 g, 1.7 mmol) are weighed in a 50 mL ampoule. , and was empty for 10 min. The solid was suspended in 10 mL of dichloromethane under argon and the mixture was allowed to stir at room temperature for 16 h in the absence of light. After filtering to remove excess silver oxide, the resulting yellow solution was evaporated and the residue was washed with hexane (2 x 15 mL), yielding product 3 (Si) 1 as a yellow oily solid (1, 48 g, 95%), whose dissolving structure corresponds to a formulation [Ag (NHC) 2] [AgBr2] that gives the syn and anti rotamers (70:30) in equilibrium. Anal. Calc. for C26H52N406Si2Ag2Br2 (948.43): C, 32.93; H, 5.53; N, 5.91%; Found: C, 32.93; H, 5.28; N, 5.93%. 1H NMR (CDCI3, 300 MHz): Anti isomer: 6 0.56 20 (t, 341, H = 7.7 Hz, 4H, SiCH2), 1.19 (t, 3JH, H = 6.9 Hz, 18H , CH3CH20), 1.88 (m, 4H, SiCH2CH2), 3.76 (s, 6H, lmz-Me), 3.78 (c, 34, H = 6.9 Hz, 12H, CH3CH20), 4, 08 (t, 34, H = 7.7 Hz, 4H, CH2Imz), 6.91 and 6.94 (d, 34, H = 1.5 Hz, 2H, Imz-H4 and Fr). IsOmero syn: 6 0.55 (t, 34.11 = 7.7 Hz, 4H, SiCH2), 1.18 (t, 3.11-1.11 = 6.9 Hz, 18H, CH3CH20), 1, 88 (m, 4H, SiCH2CH2), 3.78 (c, 3. 401 = 6.9 Hz, 12H, CH3CH20), 3.79 (s, 6H, lmz-Me), 4.06 (t, 34, H = 25 7.7 Hz, 4H, CH2Imz), 6.93 and 6.98 (d, 3s / H, H = 1.5 Hz, 2H, Imz-H4 and Fr). "G {1 H} NMR (CDCI3, 75 MHz): Anti isomer: 6 8.7 (SiCH2), 18.2 (CH3CH20), 25.6 (SiCH2CH2), 38.9 (lmz-Me), 54.1 (CH2Imz), 58.3 (CH3CH20), 121.2 and 122.1 (Imz-C4 and C5), 181.7 (Imz-C2). IsOnnero syn: 67.3 (S1CH2), 18.2 (CH3CH20), 25.2 (S1CH2CH2), 38.7 (lmz-Me), 53.9 (CH2Imz), 58.5 (CH3CH20), 121.0 and 122.0 (Imz-C4 and C5), 181.2 (Imz-C2). Diffusion coefficients DOSY-30 NMR (CDCI3, 25 ° C) in tomb at 6.0. 10-10 M2S-1 for the two rotameros. MS (ESI + / TOF, CH2C12 / Me0H / 5mM NH4HCOO): nilz 681.2542 [Ag (NHC) 2], 287.1814 [NHC + H]. 3. 4
AgBr 3 (Yes) 1 Example 14. Preparation of the silver complex 3 (51) 2. Compound 3 (Si) 2 was prepared as described for complex 3 (Si) 1 of Example 13, starting from the imidazolium salt 2 (51) 2 described in Example 5 (2.69 g, 5, 7 mmol) and Silver Oxide (0.66 g, 2.8 mmol). Complex 3 (Si) 2 was obtained as a yellow oily solid (3.07 g, 98%), whose structure in solution corresponds to a 10 [Ag (NHC) 2] [AgBr2] which gives rise to the rotameros syn and anti (70:30) in balance. Anal. Calc. for C42H68N406Si2Ag2Br2-0.7CH2C12 (1207.69): C, 42.17; H, 5.75; N, 4.81%; Found: C, 41.83; H, 5.16; N, 5.27%. 1H NMR (CDCI3, 300 MHz): Anti and syn isomers: (50.57 (m, 8H, SiCH2), 1.21 (t, 3. 4th = 7.0 Hz, 36H, CH3CH20), 1.79 (m, 8H, SiCH2CH2), 1.93 (s, 24H, Month-o-Me), 2.29 (s, 12H, Month-p- Me), 3.79 (c, 34, H = 7.0 Hz, 15 24H, CH3CH20), 4.18 (m, 8H, CH2Imz), 6.89 and 7.18 (2 xd, 3JR, H = 1.5 Hz, 2 x 4H, Imz-H4 and H5), 6.91 (s, 8H, m-Month). 13C NMR {1H} (CDCI3, 75 MHz): Anti isomer: (58.5 (SiCH2), 17.7 (CH3CH20), 21.0 (Month-p-Me), 25.7 (SiCH2CH2), 29, 1 (Month-or-Me), 53.7 (CH2Imz), 58.1 (CH3CH20), 121.6 and 123.9 (Imz-C4 and C5), 129.4 (m-Month), 134.6 ( o-Month), 135.3 (ipso-Month), 139.1 (p-Month). Isomer syn: 6 7.3 (SiCH2), 18.3 (CH3CH20), 21.0 (Month-p-Me), 25.3 20 (SiCH2CH2), 29.1 (Month-o-Me), 54, 0 (CH2Imz), 58.5 (CH3CH20), 120.9 and 122.5 (Imz-C4 and C5), 129.1 (m-Month), 134.7 (o-Month), 135.6 (ipso -Month), 139.3 (p-Month). Diffusion coefficients DOSY-NMR (CDCI3, 25 ° C) around 5.8. 10. 10 M2S-1 for the two rotanneros. MS (ESI + / TOF, CH2C12 / Me0H / 5mM NH4HCOO): m / z 889.3779 [Ag (NFIC) 2I. 25 1 == N N'mes AgBr 3 (Yes) 2 Example 15. Preparation of the silver complex 3 (51) 3. Compound 3 (Si) 3 was prepared as described for complex 3 (Si) 1 of Example 30 13, starting from the imidazolium salt 2 (Si) 3 described in Example 6 (2.50 g, 5, 2 mmol) and 35
Silver oxide (0.60 g, 2.6 mmol). Complex 3 (S1) 3 was obtained as a yellow oily solid (3.14 g, 98%), whose dissolving structure corresponds to a formulation [Ag (NHC) 2] [AgBr2] that results in the rotameros syn and anti (70:30) in balance. Anal. Calc. for C48F180N406S12Ag2Br2 (1240.89): C, 46.46; H, 6.50; N, 4.51%; 5 Found: C, 46.84; H, 6.88; N, 5.01%. 1H NMR (CDCI3, 300 MHz): Anti and syn isomers: (50.67 (m, 8H, S1CH2), 1.15 (d, 3.4th = 6.6 Hz, 24H, CH (CH3) 2), 1.20 (d, 34, Ei = 6.6 Hz, 24H, CH (CH3) 2), 1.21 (t, 34, H = 7.0 Hz, 36H, CH3CH20), 2.03 (m, 8H, SiCH2CH2), 2.36 (Sep. , 3JKH = 6.6 Hz, 8H, CH (CH3) 2), 3.85 (c, 34.11 = 7.0 Hz, 24H, CH3CH20), 4.33 (m, 8H, CH2Imz), 7, 00 and 7.20 (2 xd, 3. 4tH = 1.7 Hz. 2 x 4H, Imz-H4 and H5), 7.22 (d, 341, H = 7.7 Hz, 10 8H, m-Ph), 7.47 (t, 3JH, H = 7.7 Hz, 4H , p-Ph). 13C NMR {1H} (CDCI3, 75 MHz): Anti isomer: (57.5 (SiCH2), 18.3 (CH3CH20), 24.3 (CH (CH3) 2), 25.4 (SiCH2CH2), 28, 1 (CH (CH3) 2), 54.1 (CH2Imz), 58.6 (CH3CH20), 121.5 and 123.7 (Imz-C4 and C5), 124.2 (p-Ph), 129.7 (m-Ph), 145.6 (0-Ph), 145.9 (ipso-Ph). IsOmero syn: (5 7.3 (SiCH2), 18.3 (CH3CH20), 24.5 (CH (CH3) 2), 25.2 (SiCH2CH2), 28.3 (CH (CH3) 2), 53, 7 (CH2Imz), 58.5 (CH3CH20), 121.5 and 15 123.7 (Imz-C4 and C5), 125.7 (p-Ph), 130.5 (m-Ph), 145.6 ( 0-Ph), 145.9 (ipso-Ph). Diffusion coefficients DOSY-NMR (CDCI3, 25 ° C) in volume at 5.7. 10-10 M2S. 1 for both rotameros. MS (ESI + / TOF, CH2C12 / Me0H / 5mM NH4HCOO): m / z 973.4667 [Ag (NHC) 2] +. 20 / = \ AgBr 3 (Yes) 3 Example 16. Preparation of the silver complex 3 (A) 1. Compound 3 (A) 1 is prepared) in a manner similar to that described for complex 3 (Si) 1 of Example 13, starting from the imidazolium salt 2 (A) 1 described in Example 7 (0.80 g , 3.7 mmol) and silver oxide (0.43 g, 1.9 mmol). Complex 3 (A) 1 was obtained as a yellow oily solid (1.03 g, 88%). Anal. Calc. for C6FI11N3AgBr. 0.1C6H14 (321.56): C, 24.65; H, 3.89; N, 13.07%; Found: C, 24.95; H, 4.09; N, 13.25%. 1H NMR (CDCI3, 300 MHz): 63.09 (t, 34, H = 5.5 Hz, 2H, NH2CH2), 3.83 (s, 3H, Imz-Me), 4.14 (t, 34tH = 5.5 30 Hz, 2H, CH2Imz), 6.96 and 7.05 (2 xd, 3JH, H = 1.8 Hz, 2 x 1H, Imz-H4 and H5). 13C NMR {1H} (CDCI3, 75 MHz): 638.8 (Imz-Me), 42.9 (NH2CH2), 54.7 (CH2Imz), 121.6 and 122.1 (Imz-C4 and C5), 180.8 (Imz-C2). MS (ESI + / TOF, CH2C1) / Me0H / 5mM NH4HCOO): rniz 287.1763 [M-Br + 3H2O]. 36
/ = \ H2N N and AgBr 3 (A) 1 Example 17. Preparation of the silver complex 3 (A) 2. Compound 3 (A) 2 was prepared similarly to that described for complex 3 (Si) 1 of Example 13, starting from the imidazolium salt 2 (A) 2 described in Example 8 (3.20 g, 10.0 rnmol) and silver oxide (1.18 g, 5.1 mmol). Complex 3 (A) 2 was obtained as a yellow oily solid (3.60 g, 86%). Anal. Calc. for C14H19N3AgBr. 0.15 (C6F114) 10 (430.02): C, 41.61; H, 4.95; N, 9.77%; Found: C, 42.07; H, 4.91; N, 10.29%. 1H NMR (CDCI3, 300 MHz): 6 1.93 (s, 6H, Month-o-Me), 2.31 (s, 3H, Month-p-Me), 3.15 (t, 34H = 5, 6 Hz, 2H, NH2CH2), 4.25 (1, 34, H = 5.6 Hz, 2H, CH2Imz), 6.91 and 7.28 (2 xd, 34, H = 1.7 Hz, 2 x 1H, Imz-H4 and H5), 6.92 (s, 2H, m-Month). 13C NMR {1H} (CDCI3, 75 MHz): 6 17.7 (Month-p-Me), 21.1 (Month-o-Me), 43.1 (CH2Imz), 55.0 (NH2CH2), 121 , 4 and 122.6 (Imz-C4 and C5), 129.4 15 (m-Month), 135.3 (ipso-Month), 134.6 (o-Month), 139.6 (p-Month) , 180.2 (Imz-C2). MS (ES1 + / TOF CH2C12 / Me0H / 5mM NH4HCOO): m / z 230. 1656 [M - AgBr + H]. H2N "---- 1yN-Month AgBr 3 (A) 2 20 Example 18. Preparation of the silver complex 3 (A) 3. Compound 3 (A) 3 was prepared similarly to that described for complex 3 (Si) 1 of Example 13, starting from the imidazolium salt 2 (A) 3 described in Example 9 (3.60 g, 10 , 3 mmol) and silver oxide (1.18 g, 5.1 mmol). Complex 3 (A) 3 was obtained as a yellow oily solid (4.30 g, 90%). Anal. Calc. for C17H25N3AgBr. 0.25 (C6I-I14) (480.72): C, 46.22; H, 5.98; N, 8.74%; Found: C, 46.75; H, 5.72; N, 8.53%. 1 H NMR (CDCI3, 300 MHz): 61.11 (d, 3.41, H = 6.9 Hz, 12H, CH (CH3) 2), 1.18 (d, JH, H = 6.9 Hz, 12H , CH (CH3) 2), 2.32 (Sep. , 3. 4th = 6.9 Hz, 2H, (C1-13) 2CH), 3.17 (t, 34, H = 5.8 Hz, 2H, NH2CH2), 4.26 (t, 3JKH = 5.8 Hz, 2H, CH2Imz), 6.98 and 7.31 (2 xd, 3JH, H = 1.5 Hz, 2 x 1H, Imz-H4 and 30 H5), 7.23 (d, 3. 4tH = 7.7 Hz, 2H, m-Ph), 7.45 (t, 34, H = 7.7 Hz, 1H, p-Ph). 13 C NMR {1H} 37
5 (CDCI3, 75 MHz): 6 24.3 (CH (CH3) 2), 24.6 (CH (CH3) 2), 28.3 (CH (CH3) 2), 43.2 (NH2CH2), 55 , 0 (CH2Imz), 121.2 and 123.9 (Irriz-C4 and C5), 124.3 (m-Ph), 130.5 (ipso-Ph), 134.6 (o-Ph), 145, 6 (p-Ph), 182.8 (Imz-C2). MS (ESI + / TOF, CH2C12 / Me0H / 5mM NH4HCOO): m / z 272.2139 [M-AgBr + H]. Fi2NNy N'iPr2Ph AgBr 3 (A) 3 Example 19. Preparation of palladium complex 11 (S1) 1. In a 50 mL ampoule, the silver carbine 3 (Si) 1 described in Example 13 (0.39 g, 0.87 mmol) and PdBr2 (COD) (0.16 g, 0.43 mmol; COD = 1,5-cyclooctadiene). After the solids were subjected to vacuum for 5 min, the solid was dissolved under argon in 10 mL of dichloromethane and the resulting orange solution was allowed to stir at room temperature for 1 h. The mixture was filtered to separate the silver halide that formed as a secondary product, the resulting yellow solution was evaporated and washed with hexane (2 x 15 mL), yielding product II (Si) 1 as a powdery solid. Arnarillo color (0.65 g, 89%), whose structure in solution corresponds to the presence of the trans-syn and trans-anti rotamers (50:50) in equilibrium. Anal. Calc. for C26H52N406Si2PdBr2 (839.11): C, 37.22; H 3.25; N 6.68%; Found: C, 36.97; H, 6.07; 20 N, 6.79%. 1H NMR (CDCI3, 300 MHz): IsOrnero anti: 6 0.72 (m, 4H, SiCH2), 1.20 (t, 3J1-1, H = 6.9 Hz, 18H, CH3CH20), 2.20 ( m, 4H, SiCH2CH2), 3.81 (c, 3JH, H = 6.9 Hz, 12H, CH3CH20), 4.06 (s, 6H, Imz-Me), 4.44 (m, 4H, CH2Imz) , 6.79 and 6.88 (2 xd, 3. 1H, H = 1.7 Hz, 2 x 2H, Imz-H4 and H5). IsOmero syn: 60.72 (m, 4H, SiCH2), 1.20 (t, 3. . / H, H = 6.9 Hz, 18H, CH3CH20), 2.20 (m, 4H, SiCH2CH2), 3.81 (c, 34tH = 6.9 Hz, 12H, CH3CH20), 4.03 (s, 6H, lmz-Me), 4.44 (m, 4H, CH2Imz), 6.79 and 6.86 (2 xd, 34. 1, H = 1.7 Hz, 2 x 2H, Imz-H4 and H5). 13C NMR (1H) (CDCI3, 75 MHz): Isomer ° anti: 6 7.7 (SiCH2), 18.3 (CH3CH20), 24.4 (SiCH2CF12), 37.9 (lmz-Me), 53.1 (CH2Imz), 58.6 (CH3CFI20), 121.1 and 121.8 (Imz-C4 and C5), 169.2 (Imz-C4). IsOmero syn: 6 7.5 (SiCH2), 18.3 (CH3CH20), 24.3 (SiCH2CH2), 37.9 (Imz-Me), 52.8 (CH2Imz), 58.5 (CH3CH20), 121, 0 and 121.7 (Imz-C4 and C5), 169.2 (Imz-C2). IR (KBr): v 3080-3030 (m, arC-H st), 1525 (s, C = N st), 1380-1480 (m, arC = C st), 1080 (w, Si-OC st) , 960 (w, Si-OC st), 720-790 (m, Si-C st), 690 cm-1 (m, Si-0 st). MS (ESI + / TOF, CH2C12 / Me0H / 5mM NH4HCOO): m / z 856.1157 [M + NH41 +, 759.1635 [M-Br]. 38
Br-Pd-Br, INNSi (OEt) 3 \ ==. 1 II (Yes) 1 Example 20. Preparation of palladium complex 11 (S1) 2. 5 Compound II (Si) 2 was prepared in the same manner as compound II (Si) 1 of Example 19, starting from the silver carbine 3 (Si) 2 described in Example 14 (0.45 g, 0.81 mmol ) and PdBr2 (COD) (0.15 g, 0.41 mmol). Complex 11 (S1) 2 was obtained as a yellow powdery solid (0.83 g 97%), whose structure in solution corresponds to the presence of the trans-syn and trans-anti rotameros (56:44) in Balance. 10 Anal. Cale. C42F168N406Si2PdBr2 (1047.41): C, 48.16; H, 6.54; N, 5.35%; Found: C, 48.41; H, 6.44; N, 5.41%. 1H NMR (CDCI3, 300 MHz): Anti-Isomer: 0.47 (m, 4H, SiCH2), 1.20 (m, 18H, CH3CH20), 1.89 (m, 4H, SiCH2CH2), 2.22 (s , 12H, Month-o-Me), 2.33 (s, 6H, Month-p-Me), 3.83 (m, 12H, CH3CH20), 4.17 (m, 4H, CH2Imz), 6.70 and 6.98 (2 xd, 34, H = 1.5 Hz, 2 x 2H, Imz-H4 and H5), 6.94 (s, 4H, m-Month). Isomer syn: 6 0.73 (m, 4H, SiCH2), 1.23 15 (m, 18H, CH3CH20), 1.89 (m, 4H, SiCH2CH2), 1.91 (s, 12H, Month-o- Me), 2.43 (s, 6H, Month-p-Me), 3.81 (m, 12H, CH3CH20), 4.61 (m, 4H, CH2Imz), 6.63 and 6.93 (2 xd , 34, H = 1.5 Hz, 2 x 2H, Imz-H4 and H5), 6.81 (s, 4H, m-Month). 13C NMR {1H} (CDCI3, 75 MHz): Anti isomer Number: 6 7.1 (SiCH2), 18.4 (CH3CH20), 19.4 (Month-p-Me), 23.9 (SiCH2CH2), 29, 7 (Month-or-Me), 53.1 (CH2Imz), 58.4 (CH3CH20), 120.8 and 122.7 (Imz-C4 and C5), 128.8 (m-Month), 136.0 (ipso-20 Month), 136.6 (o-Month), 138.2 (p-Me), 169.7 (Imz-C2). Isonnero syn: 6 7.5 (SiCH2), 19.8 (CH3CH20), 21.0 (Month-p-Me), 24.3 (S1CH2CH2), 29.3 (Month-o-Me), 53.7 (CH2Imz), 58.4 (CH3CH20), 121.1 and 122.7 (Imz-C4 and C5), 128.7 (m-Month), 135.5 (ipso-Month), 135.9 (o- Month), 137.4 (p-Month), 169.6 (Imz-C2). IR (KBr): v 3080-3170 (m, arC-H st), 1620 (m, arC = C st), 1590 (s, C = N st), 1380-1450 (m, arC = C st), 1072 (w, Si-OC st), 943 (w, Si-OC st), 722-25800 (m, Si-C st), 703 cm-1 (m, Si-0 st). MS (ESI + / TOF, CH2C12 / Me0H / 5mM NH4FICOO): m / z 1064.2414 [M + NH4]. 39
f = \ N N yes (OEt) 3 II (Si) 2 Example 21. Preparation of the paladioll complex (S1) 3. 5 Compound II (Si) 3 was prepared as described for compound II (Si) 1 of Example 19, starting from silver carbene 3 (Si) 3 described in Example 15 (0.44 g, 0.70 mmol) and PdBr2 (COD) (0.13 g, 0.35 mmol). Complex II (Si) 3 was obtained as a yellow powdery solid ° (0.75 g, 95%), whose structure in solution corresponds to the presence of the trans-syn and trans-anti rotamers (60:40 ) in equilibrium. 10 Anal. Calc. C48F180N406S12PdBr2 (1131.57): C, 50.95; H, 7.13; N, 4.95%; Found: C, 50.86; H 6.63; N 5.07%. 1H NMR (DMSO-d6, 300 MHz): Anti isomer: or 0.49 (m, 4H, SiCH2), 1.13 (m, 42H, CH (CH3) 2, CH3CH20), 1.89 (m, 4H , S1CH2CH2), 2.45 (m, 4H, CH (CH3) 2), 3.72 (m, 12H, CH3CH20), 4.07 (m, 4H, CH2Imz), 7.15-7.80 (m , 10H, and H5, p-Ph, m-Ph). IsOmero syn: 6 0.58 (m, 4H, SiCH2), 1.13 (m, 42H, CH (CH3) 2, CH3CH20), 15 1.89 (m, 4H, SiCH2CH2), 2.45 (m, 4H, CH (CH3) 2), 3.72 (m, 12H, CH3CH20), 4.20 (m, 4H, CH2Imz), 7.15-7.80 (m, 10H, and H5, p-Ph, m-Ph). 13C NMR (1H) (DMSO-d6, 75 MHz): 6 8.7 (SiCH2), 14.6 (CH3CH20), 23.1 (SiCH2CH2), 23.6 (CH (C1-13) 2), 27 , 3 (CH (CH3) 2), 52.6 (CH2Imz), 57.4 (CH3CH20), 121.1 and 122.2 (Imz-C4 and C5), 123.4 (p-Ph), 129, 6 (m-Ph), 134.1 (ipso-Ph), 144.4 (o-Ph). IR (KBr): v 3030-3120 (m, arC-H st), 1625 (m, arC = C st), 20 1512 (s, C = N st), 1330-1500 (m, arC = C st) , 1123 (w, Si-OC st), 946 (w, Si-OC st), 700-800 (m, Si-C st), 685 cm-1 (m, Si-0 st). MS (ESI + / TOF, CH2C12 / Me0H / 5mM NH4HCOO): mtz 899.3888 [M - 4Et0H - Br + Me0H], 856.1127 [M - 5Et0H - Br + NH401-11 +, 776.1865 [M - 6Et0H - Brr. 25 \ (Et0) 3S1NyN'1Pr2Ph Br-Pd-Br PhiPr2-1, (INNi (OEt) II (Si) 3 Example 22. Preparation of palladium II complex (A) 1. 40
Compound II (A) 1 be prepared) as described for compound II (Si) 1 of Example 19, starting from the silver carbine 3 (A) 1 described in Example 16 (1.00 g, 3.2 mmol) and PdBr2 (COD) (0.60 g, 1.6 mmol). Complex II (A) 1 was obtained as an oily yellow solid ° 5 (0.70 g, 85%), whose characterization by NMR required its transformation into the ammonium salt, [II (A) 1] 2+ , for treatment with an excess of NH4CI and whose structure in solution corresponds to the presence of the trans-syn and trans-anti rotamers (30:70) in equilibrium. Anal. Cale. C12H22N6PdBr2 (516.57): C, 27.90; H, 4.29; N, 16.27%; Found: C, 28.10; H, 4.76; N, 16.05%. 1H NMR (DMSO-d6, 300 MHz, [II (A) 1] 2+): 10 Anti isomer: 6 2.88 (t, 34th = 5.6 Hz, 4H, CH2Imz), 3.83 (s, 6H, Imz-Me), 4.08 (t, 3JH, H = "5.6 Hz, 4H, NH2CH2), 7.67 and 7.70 (2 xs, 2 x 2H, Imz-H4 and H5). Isomer ° syn: 6 2.88 (t, = 5.6 Hz, 4H, CH2Imz), 3.74 (s, 6H, Imz-Me), 4.24 (t, 34, H = 5.6 Hz, 4H, NH2CH2), 7.40 and 7.43 (2 xs, 2 x 2H, Imz-H4 and H5). 13C NMR {1H} (DMSO-d6, 75 MHz, [II (A) 1] 2+): Anti isomer: 6 37.6 (Imz-Me), 40.8 (CH2Imz), 51.5 (NH2CH2) , 122.0 and 122.8 (Imz-C4 and 15 C6), 177.8 (Imz-C2). gHMBC- {1H, 16N} (CDCI3, 293K): 6 -190 (Num), -198 (km), -345 (NH2). MS (ES1 ÷ / TOF, CH2C12 / Me0H / 5 mM NH4HCOO): at & 453.1629 [M - HBr NH4l ÷, 436.1562 [M - Br], 355.0865 [M -HBr - Br]. 20 ir = \ H2 NyN 1 \ 1- 'Br-Pd-Br II (A) 1 Example 23. Preparation of palladium complex II (A) 2. Compound II (A) 2 was prepared as a coma described for compound II (Si) 1 of Example 19, starting from plate 3 (A) 2 carbine described in Example 17 (0.50 g, 1.2 25 mmol) and PdBr2 (COD) (0.22 g, 0.60 mmol). Corn complex II (A) 2 was obtained as an oily yellow solid (0.38 g, 88%), whose characterization for NMR required its transformation into the ammonium salt, [II (A) 212, for treatment with an excess of NH4Cly whose structure in solution corresponds to the presence of the trans-syn and trans-anti rotameros (20:80) in equilibrium. Anal. Cale. C28H38N6PdBr2 (724.87): C, 46.39; H, 5.28; N, 11.59%; 30 Found: C, 46.44; H, 5.78; N, 11.59%. 1H NMR (DMSO-d6, 300 MHz, [II (A) 2] 2+): Isomer ° anti: 6 1.85 (s, 12H, Month-o-Me), 2.32 (s, 6H, Month -p-Me), 2.93 (t, 34, H = 5.8 Hz, 41
4H, CH2Imz), 4.12 (t, 341.11 = 5.8 Hz, 4H, NH2CH2), 7.02 (s, 4H, m-Month), 7.44 and 7.67 (2 xd, 3 . 41, H = 1.8 Hz, 2 x 2H, Imz-H4 and H5). IsOmero syn: (51.91 (s, 12H, Month-o-Me), 2.36 (s, 6H, Month-p-Me), 2.96 (t, 3. 41, H = 5.8 Hz, 4H, CH2Imz), 4.19 (t, 3JitH = 5.8 Hz, 4H, NH2CH2), 6.92 (s, 4H, m-Month), 7.36 and 7 , 62 (2 xd, 3JH, H = 1.7 Hz, 2 x 2H, Imz-H4 and H5). 13C NMR {1H} 5 (DMSO-d6, 75 MHz, [II (A) 2] 2+): Anti isomer: (516.7 (Month-p-Me), 20.1 (Month-or-Me) , 43.4 (CH2Imz), 53.6 (NH2CH2), 121.9 and 122.5 (Imz-C4y C5), 128.4 (m-Month), 128.7 (ipso-Month), 134.0 (o-Month), 137.9 (p-Month), 171.5 (Imz-C2). gHMBC- {1H, 15N} (CDCI3, 293K): (5-191 (Nimz), -192 (Nirriz), -368 (NH2). MS (ESI + / TOF, CH2C12 / Me0H / 5mM NH4HCOO): m / z 644.9697 [M-Br], 563.2124 [M-Br-HBr] +. 10 / = \ NyN. month H2N Br-Pd-Br Month -NH2 N N - \ _ = / II (A) 2 Example 24. Preparation of the palladium II complex (A) 3. Compound II (A) 3 was prepared as described for compound II (Si) 1 of Example 19, starting from the silver carbine 3 (A) 3 described in Example 18 (0.50 g, 0.85 nmol) and PdBr2 (COD) (0.16 g, 0.42 mmol). Complex II (A) 3 was obtained as an oily yellow solid (0.58 g, 84%), whose NMR characterization required its transformation into the ammonium salt, [II (A) 3] 2+, by treatment with an excess of NRICI and whose structure 20 in solution corresponds to the presence of the trans-syn and trans-anti rotamers (25:75) in equilibrium. Anal. Calc. C34HSON6PdBr2 (809.03): C, 50.48; H, 6.23; N, 10.39%; Found: C, 50.07; H, 5.98; N, 10.13%. 1H NMR (DMSO-d6, 300 MHz, [II (A) 3] 2+): Anti isomer: 61.07 (d, 3.4tH = 6.9 Hz, 24H, CH (CH3) 2), 2, 26 (Sep. , 3JKH = 6.9 Hz, 4H, CH (CH3) 2), 2.89 (m, 4H, CH2Imz), 4.08 (m, 4H, NH2CH2), 7.32 (d, 3JKH = 7.9 Hz, 4H, m-25 Ph), 7.49 (t, 3JH, H = 7.9 Hz, 2H, p-Ph), 7.61 and 7.71 (2 xd, 3JH, H = 1.6 Hz, 2 x 2H, Innz-H4 and H5). IsOmero syn: 61.12 (d, 34H = 6.9 Hz, 24H, CH (CH3) 2), 2.26 (Sep. , 3JH, H = 6.9 Hz, 4H, CH (CH3) 2), 2.99 (m, 4H, CH2Imz), 4.22 (m, 4H, NH2CH2), 7.32 (d, 3. 404 = 7.7 Hz, 4H, m-Ph), 7.45 (t, 3JH, H = 7.7 Hz, 2H, p-Ph), 7.59 and 7.67 (2 xd, 34H = 1 , 5 Hz, 2 x 2H, Imz-H4 and H5). 13C {1H} NMR (DMSO-d6, 75 MHz, [II (A) 3] 2+): Anti isomer: 23.3 (CH (CH3) 2), 23.6 30 CH (CH3) 2), 27 , 2 (CH (CH3) 2), 42.5 (CH2Innz), 53.5 (NH2CH2), 121.9 and 123.9 (Imz-C4 and C5), 123.4 (m-Ph), 129, 5 (ipso-Ph), 134.5 (o-Ph), 144.9 (p-Ph), 181.3 (Imz-C2). gHMBC- {1H, 42
15N} (CDCI3, 293K): 6-187 (Nim,), --205 (Nmz), -377 (NH2). MS (ESI + / TOF, CH2C12 / Me0H / 5mM NR4HCOO): m / z 837.3255 [M-Br + HCOOH + HCOONH4r, 755.4001 [M-2HBr + 2HCOOH + NH4]. H2N '. --NyN'1Pr2Ph Br-Pd-Br II (A) 3 Example 25. Preparation of the imidazolium salt 4. Four. In a 25 mL ampoule, the starting bis (imidazolyl) methane (0.26 g, 1.7 mmol) 10 and the N- (2-bromoethyl) phthalimide (1.11 g, 4.4 mmol) were placed. After the solids were subjected to vacuum for 5 min, they were dissolved in 5 mL of dry CH3CN and the resulting solution was heated at 120 ° C for 48 h. After filtering and drying the solid °, salt 4 was obtained. 4 as a white powdery solid ° (1.05 g, 91%). Anal. Calc. for C27F124N604Br2. 2H20 (692.36): C, 46.84; H, 4.08; N, 12.14%; Found: C, 47.03; H, 4.01; N, 12.03%. 1H NMR (DMSO-d6, 300 MHz): 6 3.99 (t, 34, H = 4.6 Hz, 4H, CH2ftal), 4.53 (t, 3.44, H = 4.6 Hz, 4H , CH2Imz), 6.71 (s, 2H, CH2), 7.82 (s, 8H, o-ftal, m-ftal), 7.92 and 8.02 (2 xs, 2 x 2H, Imz-H4 and H5), 9.56 (s, 2H, Imz-H2). 13C NMR {1H} (DMSO-d6, 75 MHz): 6 37.4 (CH2ftal), 47.9 (CH2Imz), 57.8 (CH2), 121.5 and 123.4 (Imz-C4 and C5) , 122.7 (o-ftal), 131.0 (ipso-ftal), 134.1 (m-ftal), 137.6 (Imz-C2), 167.2 (C = 0). MS (ESI + / TOF, 20 CH2C12 / Me0H / NH4HCOO 5 nnM): m / z 495.1763 [M-HBr-Br]. 25 N1 1.1: 1 \ 1 r) Br-Br 4. 4 Example 26. Preparation of palladium chelate complex 5. Four. 43
The bisimidazolium 4 salt is weighed in a 15 mL ampoule with screw cap. 4 described in Example 25 (0.50 g, 0.76 mnnol) and dissolved in 1 mL of DMSO, an equivalent of palladium acetate (0.17 g, 0.76 mmol) was added on that solution. The resulting suspension was heated at 50 ° C with stirring for 2 h. After these 2 hours, the temperature was gradually increased to 110 ° C over 3 hours. The resulting reddish solution was passed () through a celite column about 2.0 cm high and 1.5 cm in diameter. After evaporating the DMSO and drying the solid, palladium chelate carbonate 5 was obtained. 4 conno a solid ° of gray color (0.49 g, 85%). Anal. Calc. for C27H22N604PdBr2. H20 (778.74): C, 41.64; H, 3.11; N, 10.79%; Found: C, 41.48; H, 10 3.23; N, 10.95%. 1H NMR (DMSO-d6, 300 MHz): 3.80-4.10 (2 xm, 2 x 2H, CH2ftal), 4.11 and 5.15 (2 xm, 2 x 2H, CH2Imz), 6.25 (m, 2H, CH2), 7.33 and 7.52 (2 xs, 2 x 1H, Imz-H4 and H5), 7.60 (s, 8H, o-ftal and m-ftal). 13C NMR {1H} (DMSO-d6, 75 MHz): 6 37.5 (CH2ftal), 48.5 (CH2Imz), 62.1 (CH2), 120.8 and 121.3 (Imz-C4 and C5) , 122.3 (o-ftal), 130.7 (ipso-ftal), 133.6 (m-ftal), 159.6 (Imz-C2), 166.7 (C = 0). MS (ESI + / TOF, CH2C12 / 5 mM MeOHNH4HCOO): 15 m / z 761,039 [M + H], 697,126 [M - HBr + NH4] +, 617,086 [M - 2HBr +) -N Br L-1 0 0 5. 4 Example 27. Preparation of palladium chelate complex III (A) 4. 20 The palladium complex 5 is weighed in a 25 mL ampoule. 4 described in Example 26 (1.00 g, 1.3 mmol) and dissolved in 2 mL of dry CH3CN. On the suspension formed, 40 equivalents of hydrazine (2.50 mL, 52.0 mmol) were added, giving a clear solution. After one hour of reaction at room temperature, the phthanylhydrazine 25 formed was filtered, the solvent was evaporated and washed) with hot THF using a soxhlet equipment, yielding product III (A) 4 curio a solid ° beige (0.50 g , 82%). Anal. Lime. for C11H201 \ 160PdBr2. H20 (518.54): C, 2548; H, 3.89; N, 16.21%; Found C, 25.46; H, 4.02; N, 16.23%. 1H NMR (DMSO-d6, 300 MHz): 53.03 (wide s, 4H, CH2Imz), 4.23 (wide s, 4H, NH2CH2), 4.70 (wide s, 4H, NH2), 6.34 (s, 2H, CH2), 7.62 and 7.69 (2 xs, 2 x 30 1H, Imz-H4 and Fr). 13C NMR {1H} (DMSO-d6, 75 MHz): 6 40.3 (CH2Imz), 49.3 (NH2CF12), 44
61.3 (CH2), 120.6 and 122.7 (Imz-C4 and C5), 152.0 (Imz-C2). gHMBC- {1H, 15N} (DMSO-d6, 293K): 5197 (Nim,), —203 (Nim,), —381 (NH2). IR (KBr): v 3393 (NH2 st), 3030-3100 (m, arC-H st), 1590-1610 (m, arC = C st), 1530 (s, C = N st), 1395-1480 cm -1 (m, arC = C st). MS (ESI + / TOF, CH2C12 / Me0H / 5mM NH4HCOO): miz 420.9814 [M-Br], 365.1714 [M-2HBr 5 + Na], 339.0556 [M-HBr-Br]. eN) —N Pd r Br / 'Br -1 H2N NH2 Example 28. Preparation of PMC (S1) 11. 10 III (A) 4 In a 25 mL Eppendorf vial 15 mg of silicon-coated PMs (Silica-Adembeads 300 nm from Ademtech) were added: nude of maghemite (y-Fe203); metal oxide content> 70%, magnetization of saturation: 40 emu / g; grain density: 1.8-2 g / cm3; specific surface area 10 m2 / g), 1 mL of Tx (Tx = aqueous solution of TritonTm X405 at 15 0.21% v), 1 mL of ethanol and 175 pL of a 30% aqueous solution of ammonia, to then sonicate the sample using a 200 W model 200200 UPS Hielscher instrument, for 5 min and half its maximum power. In another vial the complex l (Si) 1 described in Example 10 (93.75 pmol) was weighed and dissolved in 4.5 mL of ethanol. Under mechanical agitation (using a Bioshake iQ agitator / heater from Qlnstruments) over 20 the suspension of PMs was added dropwise drop the solution of the complex for 2.5 h, at 25 ° C and 750 rpm and sonicating every 15 min to favor the dispersion of the particles. It was then heated to 40 ° C and allowed to stir 1 h more at 750 rpm. With the help of an external magnet, the solution was decanted and the particles were washed with ethanol, with 5 mL fractions until the washings were colorless, then washed with 25 Pluronic0 F127 (0.30% v) (3 x 5 mL ) and finally with Tx (3 x 5 mL). PMC (S1) 11 was obtained as a brown powdery solid, which was stored at 5 ° C dispersed in 5 mL of 0.21% Tx. ICP-MS: 0.28% w Pd. IR ATR: v 1620 (m, arC = C st), 1502 (s, C = N st), 1380-1480 (m, arC = C st), 800 cm-1 (m, Si-C st). TEM: magnetic stress particles of size between 280-340 nm with an average thickness 30 of the silicon coating of 1.5 nm for the silica layer. Four. Five
PMC (Yes) 11 Example 29. PMC Preparation (SI) 12. -N 5 The PMC (Si) I2 were prepared as described for PMC (Si) 11 in Example 28, but using the complex l (S1) 2 described in Example 11. They were obtained as a brown, powdery solid, which is preserved at 5 ° C dispersed in 5 mL of 0.21% Tx. ICP-MS: 0.77% w Pd. IR ATR: v 1615 (m, arC = C st), 1501 (s, C = N st), 1380-1480 (m, arC = C st), 780 cm-1 (m, Si-C st). TEM: spherical magnetic particles of tamatium 10 comprised between 265-345 nm with an average thickness of the silica coating of 2.0 nm for the silica layer. PMC (Yes) 12 15 Example 30. PMC Preparation (SI) 13. PMC (S1) 13 were prepared as described for PMC (Si) 11 in Example 28, but using the complex l (Si) 3 described in Example 12. They were obtained as a powdery solid marrem color, which was stored at 5 ° C dispersed in 5 mL of 0.21% Tx. 20 ICP-MS: 0.66% w Pd. IR ATR: v 1560-1640 (m, arC = C st), 1330-1480 (m, arC = C st), 770 cm- (m, Si-C st). TEM: spherical magnetic particles of tamatium between 280-350 nm. 46
—0, HO; Yes N N ,. —0 and Pr2Ph 1 — Pd — I PMC (Yes) 13 Example 31. Preparation of PMC (S1) 111. 5 The PMCs (Si) 111 were prepared as described for PMCs (Si) 11 in Example 28, but using the complex II (Si) 1 described in Example 19. A powdery brown solid, which is preserved) at 5 ° C dispersed in 5 mL of 0.21% Tx was obtained. ICP-MS: 0.24% w Pd. IR ATR: v3080-3150 (m, arC-H st), 1380-1530 (m, C = N st, arC = C st). TEM: spherical magnetic particles of size between 260-330 10 nm. LOSI 0 —0 'and Br — Pd-Br —0, -If 1-0 ‘= _ / PMC (S1) 111 Example 32. Preparation of PMC (S1) 112. The PMC (S1) 112 were prepared as described in PMC (S1) 11 in Example 28, but using the complex II (S1) 2 described in Example 20. They were obtained as a brown powdery solid, which was stored at 5 ° C dispersed in 5 mL of 0.21% Tx. ICP-MS: 0.51% w Pd. IR ATR: v 3060-3200 (m, arC-H st), 1620-1650 (s, arC = C 20 st), 1350-1520 (m, C = N st, arC = C st). TEM: spherical magnetic particles of tamatium between 290-350 nm. 47
a) / - = \ C: I; Yes, NyN, month —0 0. 0 Br — Pd-Br = in F ° C) 3Si -'----. 'N N' PMC (Yes) 112 Example 33. Preparation of PMC (S1) 113. Month —N 5 The PMC (S1) 113 were prepared as described for PMC (Si) 11 in Example 28, but using the complex II (51) 3 described in Example 21. They were obtained as a powdery brown solid, which was stored at 5 ° C dispersed in 5 mL of 0.21% Tx. ICP-MS: 0.43% w Pd. IR ATR: v 3050-3180 (m, arC-H st), 1620-1650 (s, arC = C st), 1380-1520 (m, C = N st, arC = C st). TEM: spherical magnetic particles of tamarum 10 comprised between 280-360 nm. 0, / = \ N. . 0 'and' Pr2Ph Br — Pd-Br 0, iPr2Ph 1: 2 (PMC (Si) 113 Example 34. Prepared & from PMC (A) I11. 15 In a 5 mL vial, 15 mg of PMs coated with crosslinked polystyrene functionalized with carboxylic acid groups (Carboxyl-Adembeads 200 nm from Ademtech: nude of maghemite (y-Fe203), metal oxide content> 70%, were weighed. Saturation nnagnetization: 40 emu / g; 300 mmol COOH / g of MNPs, density of COOH groups on 20 surface: 20 pmol / m2, grain density: 1.8-2 g / cm3; specific surface 15 m2 / g) which were suspended in 1.5 mL of Tx / Me0H (2: 1; Tx = 0.21% TritOnTm X405 aqueous solution) and sonicated with a 200 W UPS200S Hielscher model for 5 min. its maximum power. On the other hand, a DMF solution of complex 11 (A) 1 described in Example 22 (45 pmol) was prepared. 25 250 pL of both mixtures were placed in six Eppendorf 1.5 mL vials used, so that 48
each contained 0.75 pmol of COOH groups and 15.0 pmol of NH groups, and on each one 200 pL of a solution of carbodiimide CHMC (N-cyclohexyl-N '- (24N-methylmorpholinolethyl) carbodiimide) was added. in Tx ([CHMC] = 0.03 m. Each Eppendorf vial was completed with 350 pL of Tx / Me0H (2: 1) to a final volume of 1 mL in 5 each vial. Once the six samples were prepared, they were placed under mechanical agitation (using a Stuart rotator SB2 carousel stirrer) at 20 rpm for 16 h at room temperature. After the solutions were decanted with the help of a magnet, the Table 3 samples were washed successively with an aqueous solution of 10 mm NaOH (2 x 1 mL), with Tx (2 x 1 mL), with a THF / Tx mixture (2 : 1) in fractions of 1 mL 10 until the wash waters were colorless. PMC (A) II1 was obtained as a brown powdery solid, which was stored at 5 ° C dispersed in 1 mL of 0.21% Tx. ICP-MS: 0.26% w Pd. IR (KBr): v2900-3000 (m, arC-H st), 1723 (C = 0 st), 1601 (m, arC = C st), 1493 (s, C = N st), 1450-1480 (m , arC = C st), 1260 cm-1 (CN St (amide)). pH at the isoelectric point of potential Z: P. I. = 4.8 [P. I. (Starting PMs) = 2.9]. TEM: 15 spherical magnetic particles of size between 160-230 nm. N— H and El N "Br — Pd-Br k = 1 / IN PMC (A) 111 Example 35. Preparation of PMC (A) I12. The PMC (A) II2 was prepared as described for PMC (A) II1 in Example 34, but using the complex II (A) 2 described in Example 23. They were obtained as a powdery brown solid, which was stored at 5 ° C dispersed in 1 mL of 0.21% Tx. ICP-MS: 0.54% w Pd. IR (KBr): v 2900-3000 (m, arC-H st), 1724 (C = 0 st), 1601 (m, 25 arC = C st), 1492 (s, C = N st), 1450-1480 (m, rC = C st), 1260 cm-1 (CN St (amide)). pH at the isoelectric point of potential Z: P. one. = 4.3 [P. I. (Starting PMs) = 2.9]. TEM: spherical magnetic particles of size between 190-270 nm. 49
/ = \ N -N N H and N. Br — Pd — Br 0 PMC (A) II2 Example 36. Preparation of PMC (A) I13. 5 The PMCs (A) 113 were prepared as described for PMCs (A) 111 in Example 34, but using the complex 11 (A) 3 described in Example 24. They were obtained as a brown, powdery solid, which is preserved at 5 ° C dispersed in 1 mL of 0.21% Tx. ICP-MS: 0.36% w Pd. IR (KBr): v 2900-3000 (m, arC-H st), 1723 (C = 0 st), 1601 (m, arC = C st), 1493 (s, C = N st), 1450-1480 ( m, arC = C st), 1260 cm-1 (CN St (amide)). pH at 10 the isoelectric point of potential Z: P. ;. = 4.6 [P. I. (Starting PMs) = 2.9]. TEM: spherical magnetic particles of tamarium between 180-250 nm. N N. H and s'Pr2Ph Br — Pd — Br H lPr2Ph N PMC (A) II3 15 Example 37. Preparation of PMC (A) 1114. PMC (A) 1114 were prepared as described for PMC (A) 111 in Example 34, but using the complex 111 (A) 4 described in Example 27. They were obtained as a brown powdery powder, which Sc kept at 5 ° C dispersed in 1 mL of 0.21% Tx 20. ICP-MS: 0.81% w Pd. IR (KBr): v 2923-2970 (m, arC-H st), 1698 (C = 0 st), 1601-1650 (m, arC = C st), 1538 (s, C = N st), 1450- 1480 (m, arC = C st), 1272 cm-1 (CN St (amide)). pH at the isoelectric point of potential Z: P. I. = 6.2 [P. I. (Starting PMs) = 2.9]. TEM: spherical magnetic particles of size between 190-250 nm. fifty
_ _ e HN— \ N. , - 1 2 Br,) —N? Pd> (7. 0_ Br ') - N / --- N. HN— / 0 PMC (A) III4 Example 38. Testing of catalytic activity of the PMCs of this invention in Suzuki-Miyaura reactions. 5 The catalytic tests were carried out in a glove box ("La petite" model 815-PGB of Plaslabs INC), in the absence of oxygen, in sterilized 1.5 mL Eppendorf single-use vials containing 1 mL of a suspension of the supported palladium catalyst (ii) in a 9: 1 mixture of an aqueous solution of 10 TritOnrm X405 at 0.21% by volume and TM :, the corresponding haloarene (4-bromine or 4-chlorotoluene), Phenylboronic acid (molar ratio with respect to haloarene 1: 1,2), potassium carbonate (molar ratio with respect to haloarene 1: 3) and naphthalene as internal standard (0.5 mmol). In all cases 2.5 mg of PMCs were used and the amounts of the substrates were adjusted to reach a palladium load of 0.05 mol 15% [Pd] for the PMC (S1) 11-3 described in Examples 28 at 30 and 0.024 mol% [Pd] for the remainder described in Examples 31 to 37, with respect to haloarene. These mixtures were sonicated in a bath for one minute (Elmasonic S40, 37 kHz sonication frequency). Then the vials were placed inside the glove box on the support of a previously thermostated mechanical agitator (Bioshake iQ de Qlnstruments) with temperature control at 65 ° C for bromotoluene activation and at 80 ° C for chlorotoluene activation . Once the vials were placed, the reaction time began to be measured. The progress of the reaction was continued by periodically removing samples that were analyzed by gas chromatography (HP-5890 Series II Instrument chromatograph with flame ionization detector (FID); DB-WAX polar capillary column with a polyethylene glycol film of 0, 25 pm thick and 30 meters long and 0.25 mm in diameter; 250 ° C injector, 260 ° C detector, 180 ° C oven isothermal (bromotoluene) or 120 ° C isothermal for 5 min and temperature ramp at 60 ° C / min up to 200 ° C (chlorotoluene). For GC-FID monitoring, 1 pL of the 51 was taken
solution and diluted) in the reaction solvent to 10 pL, from there take) 1 pL which was injected directly. The conversion is determined from the concentration of haloarene present in the reaction mixture, using the naphthalene peak as internal standard and relative to the calibration line determined for 4-iodotoluene. The coupling product was identified by 1 H NMR. All experiments were performed at least in duplicate. Reaction targets were also made, without adding PMCs, to rule out possible false results caused by palladium contamination of substrates, bases, solvents or starting PMs without supported complex. Table 3 collects the results obtained with the PMCs described in Examples 28 to 37. 10 Example 39. Catalytic activity assays of the PMCs of this invention in Heck-Mizoroki reactions. The catalytic tests were carried out in the manner described in Example 38, but with 15 4-iodotoluene, methyl acrylate (molar ratio with respect to haloarene 1: 1.2), triethylamine (molar ratio with respect to haloarene 1: 1 ) and naphthalene as internal standard (0.5 mmol), with the mechanical stirrer previously thermostated at 90 ° C and with the chromatograph configured as indicated in Example 38 for 4-bromotoluene. Table 4 shows the results obtained with the PMCs described in Examples 28 to 37. Example 40. Evaluation of the recyclability of the PMCs of this invention in coupling reactions of Suzuki-Miyaura and Heck-Mizoroki. Once the reaction was over, the vials were placed within the magnetic field of a 25 neodymium magnet (Supermagnete) for 5 min in order for the PMCs to be deposited on the side of the Eppendorf oriented towards the magnet. Subsequently, the solutions were decanted with the products and the resulting PMCs were washed with THF (5 x 1 mL) and Tx (5 x 1 mL; Tx = aqueous solution of TritonTm X405 at 0.21% v). Next, 1 mL of Tx / THF (9: 1) 30 containing a new substrate mixture was added to the vial with the recovered MNPs in order to restore the initial reaction concentrations described in each case in Examples 38 and 39. Once the reagents were added, proceed) AS indicated in each case in Examples 38 and 39. The operation was repeated a dozen times (13 uses of the catalyst counting the initial reaction) always under the same conditions and same reaction time. From Figure 35 to Figure 6 a selection of graphic representations of some of the kinetic profiles obtained for the PMC (Si) 112 described in Example 32, 52 is shown.
PMC (A) II3 described in Example 36 and PMC (A) III4 described in Example 37 in Suzuki-Miyaura reactions with both 4-bromotoluene and 4-chlorotoluene which were carried out as described in Example 38 Figure 7 and Figure 8 show a selection of graphic representations of some of the kinetic profiles 5 obtained for the PMC (Si) I3 described in Example 30, PMC (Si) 112 described in Example 32, PMC (A) 113 described in Example 36 and PMC (A) III4 described in Example 37 in the reactions of Heck-Mizoroki with 4-iodotoluene which were carried out as described in Example 39. 10 Example 41. Quantification of palladium leachate from the PMCs of this invention in coupling reactions of Suzuki-Miyaura and Heck-Mizoroki. Quantitative analyzes of palladium have been carried out by ICP-MS (Inductively coupled plasma mass spectrometry) of the separated solutions 15 both in the initial reactions described in Examples 38 and 39 and in the successive reactions in the series of recycled described in Example 40. The analyzes were carried out of the solutions separated after the first one (recycling n ° 0-1), the second (recycling n ° 1-2), the third (recycling n ° 2-3), the fourth to the twelfth combined (recycling n 3-11) and the third use of the catalyst (recycled n ° 12). 20 The palladium content of the PMCs recovered at the end of each recycle series was also quantified by ICP-MS. In the quantification of palladium by ICP-MS, at least 3 independent analyzes have been carried out in an Agilent 7700x device (detection limit 1ppb (pg / L); sample injection mode: Helium 4.3 mL / minute; values accepted [RSD] under 10%). The samples were prepared by taking a fraction of known mass of solid ° obtained by direct evaporation of the corresponding suspension or solution and dissolving it in acidified medium (nitric acid / hydrochloric acid 3: 1). Table 5 shows an illustrative selection of the percentage of initial palladium found in separate solutions and that lost by some of the PMCs of this invention (specifically the PMC (Si) I12 described in Example 32, the 30 PMC (A) II3 described in Example 36 and the PMCs (A) III4 described in Example 37) in the initial Suzuki-Miyaura reactions and subsequent reuse described in Examples 38 and 40, respectively, together with the conversion decreases (always measured in each case at the same time of reaction) recorded in the consecutive reactions of each series and expressed in percentage points. Table 6 shows an illustrative selection of the percentage of initial palladium found in separate solutions and that lost by some of the PMCs of this invention (specifically the 53
PMC (S1) 13 described in Example 30, the PMC (Si) 112 described in Example 32, the PMC (A) II3 described in Example 36 and the PMC (A) III4 described in Example 37) in the reactions of Heck-Mizoroki initial and successive reuse described in Examples 39 and 40, respectively, together with the conversion decreases (measured in 5 cases always at the same time of reaction) recorded in the consecutive reactions of each series and expressed in percentage points ales Example 42 Determination of the initial productivity and activity values (TON ° and TON, of cumulative productivity (TON, -) of average activity (TOFAv) and 10 of palladium content found in the products (in ppm mass) using the PMCs of this invention in coupling reactions of Suzuki-Miyaura and Heck-Mizoroki. The TON ° values have been determined taking into account the molar relationship of the limiting substrate with the palladium incorporated with each PMC and the conversion reached at the time specified in each case (Table 7 to Table 9), in the reactions described in the Examples 38 and 39. The TOF0 value for each PMCs is the relationship between the corresponding value of TON () and the time, expressed in hours, to achieve that productivity in the reactions described in Examples 38 and 39. The TONT value for 20 each PMCs is the sum of the TON value () and the TON values recorded in each of the 12 reuses described in Example 40. The TOFAv value for each PMCs is the arithmetic mean of the TOF0 and the TOF values recorded in each of the 12 reuses described in Example 40. The content of palladium in the products after the 13 uses of each PMC has been determined taking into account the value of TONT 25 reached in each case, the molecular weight of the product obtained, the quantification described in Example 41 of the leaching of the metal at separate solutions of the PMCs in the recycles described in Example 40 and the initial metal charge used in each series. The palladium content in the products is expressed in parts per million (ppm) as the ratio of metal masses found in the solutions and of the total product formed. Table 7 shows the values found in the reactions of Suzuki-Miyaura with 4-bromotoluene for some of the PMCs of this invention, specifically the PMC (Si) I11-3, PMC (A) I11-3 and PMC (A) 1114 described in Examples 31 to 37. Table 8 shows the values found in Suzuki-Miyaura reactions with 4-chlorotoluene for some of the PMCs of this invention, specifically 35 PMC (Si) 111-3, PMC (A) I11-3 and PMC (A) 1114 written in Examples 31 to 37. Table 9 shows the values found in the reactions of Heck-Mizoroki with 4-iodotoluene 54
for the PMCs described in Examples 28 to 37. Example 43 Ana! Isis TEM of the PMCs of this invention and of the separate solutions with the catalytic products. 5 The PMCs of this invention described in Examples 28 to 37 have been inspected by TEM (Transmission Electron Microscopy), both before use in the activity tests described in Examples 38 and 39 and of the PMCs recovered at the end of series of recycles described in Example 40, as well as samples 10 prepared from the separate solutions in those recycled ones. The TEM analyzes have been carried out using a JEOL JEM 2100 microscope that operates at a voltage of 200 kV, equipped with double inclination sample holder ± 42 / ± 300, with a resolution between 2.5 A points and an EDS microanalysis system ("x-ray energy dispersive spectrocopy") with an OXFORD INCA instrument. Alternatively, a HITACHI H7650 microscope has been used that operates at a voltage of 120 kV, equipped with a GATAN camera of 11 Mpx resolution. Two different procedures for preparing PMC samples were followed depending on the equipment used for the measurement. For the JEOL JEM 2100 equipment, some milligrams of the corresponding PMCs were embedded in a low viscosity epoxy resin known as Spurr, which consists of four components: the resin itself (ERL 4206, 50 mL), plasticizer (DER 736, 30 mL), hardener (NSA, 130 nnL) and accelerator (DMAE, 2 mL). The resin was allowed to cure and harden for two days, after which it was cut into very thin sheets by using an ultramicrotome (Reichert-Jung, Ultracut-E model. ). These sheets were deposited on 3 mm diameter copper grids coated with carbon (400 mesh). Alternatively, for the HITACHI H7650 microscope, the sample preparation is carried out) by preparing dispersions of the PMCs in methanol or water (5-10 pL, 0.25-0.5 rng / nnL) on 3 mm diameter copper gratings Coated with carbon (400 mesh) allowing deposition to occur by evaporation. Samples of the separate catalytic solutions of the PMCs were analyzed interchangeably in one of the two equipment and their preparation was made by adding 5 drops of the catalytic solution on 3 mm diameter copper grids coated with carbon (400 mesh) leaving that deposition occurs by evaporation. The absence of metallic palladium in the samples was determined by EDS, inspecting the existence of the characteristic emission lines of the L layer of this metal at 2.83 KeV (Lai) and 3.03 KeV (431). The comparison and analysis of the images obtained from the PMCs, whole or cut with ultramicrotome, before and after their 55
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HETEROGENEIZED NHC PALADIO COMPLEXES AND THEIR USES AS RECOVERY CATALYSTS SECTOR OF THE TECHNIQUE 5 The invention is based on the chemical and pharmaceutical sector, more specifically on catalysts for organic synthesis processes based on metal complexes, and more specifically on N-heterocyclic carbine complexes supported palladium, magnetically separable after use, reusable and resistant to metal leaching, and in use 10 in carbon-carbon coupling reactions. STATE OF THE TECHNIQUE As a result of the easy access of the substrates to their active centers and to the modifiable and controllable environment of these, catalysts based on metal complexes are characterized by their high activity and selectivity in many chemical processes that are carried out in mild conditions in homogeneous phase. However, at present the industrial use of homogeneous catalysis applied to the production of pharmaceuticals, agrochemicals and other products of fine chemicals, is quite limited. The 20 main reasons for the above are, on the one hand, the cost of the complexes and, on the other, the greatest difficulty in separating them from the products compared to heterogeneous catalysts. These obstacles are especially relevant with platinum group metal complexes (Pt, Pd, Ir, Rh, Os, Ru), on which, in addition, there are environmental and sanitary guidelines and regulations that drastically restrict the permissible levels of contamination by metals in many productions (e. g. , European Medicines Agency 2008). There is, therefore, a huge potential market for metal catalysts that combine the advantages of homogeneous phase catalysts (i. and. , high activity and selectivity in 30 mild conditions) with those of the heterogeneous phase (i. and. , high productivity and easy recovery and recycling). A general classification of the strategies that have been explored so far includes: multi-phase catalysis or confinement of the homogeneous catalyst in a different phase from the substrate and products, including aqueous phases, ionic liquids, supercritical fluids or fluorinated solvents; ii) use of 35 nanofiltration membranes with enlarged molecular weight catalysts by means of their immobilization to soluble supports such as dendrimeros, polinneros or polysisesquioxanes; 2