The development of a Cu(l)/bis(pyridyl)-N-alkylamine catalyst system for selective alcohol oxidation

Abstract

Different bis(pyridyl)-N-alkylamine ligands, with the general formula of (2-C5H3NR)2NR′, (L1): R = H, R′ = Me; (L2): R = H, R′ = benzyl; (L3): R = H, R′ = methylcyclohexyl; (L4): R = H, R′ = neopentyl; (L5): R = Me, R′ = Me, were prepared by employing a modified method, which involved base-mediated N-alkylation. These ligands were characterised with Fourier transform infrared (FT-IR) and nuclear magnetic resonance (NMR) spectroscopic techniques. We optimised our catalyst system, L3/Cu(MeCN)4OTf/TEMPO·/NMI, through the evaluation of the combination of different bis(pyridyl)-N-alkylamine ligands (L1-L5), CuI/CuII-precursors and N-substituted imidazole bases on the oxidation of 1-octanol to 1-octanal. Thereafter, initial rate kinetic studies were used to evaluate the effect of [1-octanol], [TEMPO·], [NMI] and [L3Cu] on the initial rate of the oxidation reactions. These results allowed us to obtain the concentrations required for optimal catalytic activity in the oxidation of 1-octanol: 0.2 M [1-octanol], 20 mM [TEMPO·], 20 mM [NMI] and 20 mM [L3Cu]. Furthermore, electrospray ionisation mass spectrometry (ESI-MS) studies were used to investigate the formation of the proposed Cu-based intermediates during the oxidation of benzyl alcohol. These studies allowed us to provide experimental evidence for the formation of an unstable ion at m/z 363, consistent with a [(L1)(NMI)CuII-OOH]+ intermediate, which is a key intermediate in the alcohol oxidation reaction. In addition, an ion was also observed at m/z 945, consistent with the formation of a CuII-dimeric species, in the absence of the alcohol substrate. The CuII-dimeric species disappeared after the addition of the alcohol substrate and no further formation was observed during the oxidation reaction. This observation highlighted its formation as a result of CuII accumulation in the absence of substrate. The kinetic studies, in combination with the ESI-MS studies, were used to determine the applicability of the previously proposed mechanistic pathways on our catalyst system. The identified Cu-based intermediates were summarised in a possible reaction pathway for our catalyst system, which supports previously proposed mechanistic pathways. Our bis(pyridyl)-N-alkylamine/CuI/TEMPO·/NMI catalyst system could be used for the oxidation of a variety of primary alcohols to the corresponding aldehydes, using readily available reagents and synthetically relevant reaction conditions. No over-oxidation to the corresponding carboxylic acid was observed for these alcohol substrates. The careful choice of reaction solvent allowed for the oxidation of 4-hydroxybenzyl alcohol, a substrate that proved problematic in previous studies. In the case of 2-pyridinemethanol as substrate, experimental evidence showed that catalytic activity is diminished due to the competitive inhibition of the catalyst by the alcohol substrate. Matrix-assisted laser desorption-ionisation mass spectrometry (MALDI-MS) analysis of the reaction mixture in the presence and absence of TEMPO· and NMI showed the formation of identical mass fragments. An important mass fragment was observed at m/z 563, consistent with the formation of a Cu2-hydroxo dimer, where the alcohol substrate acts as ligand.

Verskillende bis(piridiel)-N-alkielamien ligande, met ’n algemene formule van (2-C5H3NR)2NR′, (L1): R = H, R′ = Me; (L2): R = H, R′ = bensiel; (L3): R = H, R′ = metielsikloheksiel; (L4): R = H, R′ = neopentiel; (L5): R = Me, R′ = Me, is gesintetiseer deur gebruik te maak van ’n gemodifiseerde sintesemetode. Hierdie metode behels ’n basis-gemedieerde N-alkileringsreaksie. Fourier transform infrarooi- (FT-IR) en kern magnetiese resonans- (KMR) spektroskopiese metodes is vir die karakterisering van die ligande gebruik. Tydens die optimering van ons katalisatorsisteem, L3/Cu(MeCN)4OTf/TEMPO·/NMI, is die effek van die kombinasie van verskillende bis(piridiel)-N-alkielamien ligande (L1-L5), CuI/CuII-voorgangers en N-gesubstitueerde imidasool basisse op die oksidasiereaksie van 1-oktanol na 1-oktanaal geëvalueer. Aanvanklike tempo kinetiese studies is gebruik om die effek van [1-oktanol], [TEMPO·], [NMI] en [L3Cu] op die aanvanklike tempo van die oksidasiereaksie te evalueer. Hierdie resultate het ons in staat gestel om die konsentrasies wat vir optimale katalitiese aktiwiteit tydens die oksidasie van 1-oktanol benodig word, te identifiseer: 0.2 M [1-oktanol], 20 mM [TEMPO·], 20 mM [NMI] en 20 mM [L3Cu]. Verder is elektronsproei-ionisasie massaspektrometriese-(ESI-MS) studies gebruik om die voorgestelde Cu-gebaseerde intermediêre, wat tydens die oksidasie van bensielalkohol gevorm het, te identifiseer. Hierdie studie het eksperimentele bewyse vir die vorming van ’n belangrike ioon tydens die alkoholoksidasie reaksie verskaf. Die belangrike ioon kom by m/z 363 voor, wat ooreenstem met die onstabiele [(L1)(NMI)CuII-OOH]+ intermediêr. Verder, in die afwesigheid van die alkoholsubstraat, is ’n ioon by m/z 945 waargeneem. Die ioon stem ooreen met ’n CuII-dimeriese spesie wat verdwyn wanneer die alkoholsubstraat bygevoeg word en is nie verder gedurende die oksidasiereasie waargeneem nie. Hierdie waarneming bevestig dat die dimeriese spesie as gevolg van CuII-akkumulasie, in die afwesigheid van die substraat, vorm. Die kinetiese studies, in kombinasie met die ESI-MS studies, is gebruik om sodoende die toepaslikheid van voorheen voorgestelde meganistiese roetes op ons katalisatorsisteem te bepaal. Ons moontlike reaksieroete is saamgestel uit die geïdentifiseerde Cu-gebaseerde intermediêre, wat tydens die oksidasiereaksie voorkom, en hierdie roete ondersteun ook vorige meganistiese roetes. Ons bis(piridiel)-N-alkielamien/CuI/TEMPO·/NMI katalisatorsisteem is vir die oksidasie van primêre alkohole na die ooreenstemmende aldehiede gebruik. Geredelik beskikbare reagense is in die oksidasiereaksies gebruik wat by kamertemperatuur en oop tot lug uitgevoer is. Geen oor-oksidasie na die ooreenstemmende karboksielsure is vir hierdie alkoholsubstrate waargeneem nie. Ons katalisatorsisteem in kombinasie met ‘n gepasde oplosmiddel, is gebruik om een van die substrate wat voorheen probleme veroorsaak het, 4-hidroksibensiel-alkohol, suksesvol te oksideer. Ons het ook eksperimentele bewyse vir die inhiberende effek van die alkoholsubstraat tydens die oksidasie van 2-piridienmetanol, gevind. Matriks-geassisteerde laser desorpsie-ionisasie massaspektrometriese-studies (MALDI-MS) is gebruik om sodoende die reaksiemengsel in die teenwoordigheid en afwesigheid van TEMPO· en NMI te ontleed. Identiese massafragmente is in beide gevalle gevind, met ’n belangrike fragment wat teenwoordig is by m/z 563. Hierdie fragment stem ooreen met die vorming van ’n Cu2-hidrokso-dimeer, waar die alkoholsubstraat as die ligand optree.