SiliaCat® TEMPO: An Effective and Recyclable Oxidizing Catalyst Annie Michauda, Valerica Pandarusa, Lynda Tremblaya, Rosaria Ciriminnab, Mario Pagliarob, and François Bélanda* a SiliCycle®Inc. (www.silicycle.com), 2500 Parc-Technologique Blvd, Quebec City (Quebec), Canada, G1P 4S6 b Istituto per lo Studio dei Materiali Nanostrutturati, CNR, via Ugo La Malfa 153, 90146 Palermo, Italy (*[email protected])

Reusability

Minimal leaching and the robustness of the organoceramic matrix allows it to be recycled several times for further uses. Introduction Homogeneous vs. Heterogeneous

Over the years, chemists have developed various oxidizing agents such Compared to homogeneous TEMPOs, SiliaCat TEMPO provides as pyridinium chlorochromate (PCC), MnO , Dess-Martin 2 significantly superior yields in basic conditions and comparable at periodinane, or Swern oxidation conditions. Although these reagents neutral pH. provide aldehydes with limited over-oxidation to carboxylic acids, they carry drawbacks such as hazardous and specific handling and Reusabilitya Time (min) Conversion (%) unwanted toxicity from residual metal contamination. 1st 30 100

2nd 30 100

We have developed a silica-based version of the 2,2,6,6- … … …

Tetramethylpiperidin-1-oxyl (TEMPO) nitroxyl radicals as an 8th 30 / 60 95 / 100 alternative reagent for such type of transformations. 9th 30 / 60 97 / 100 pH SiliaCat TEMPO 4-MeO-TEMPO 4-Oxo-TEMPO

th 7.5 91% 99% 45% 10 30 / 60 90 / 100 a 9.0 98% 55% (40%) 73% SiliaCat TEMPO [1] is a heterogeneous catalysts made from a leach- a SiliaCat TEMPO is recycled by post-reaction filtration, DCM washes and air drying. a resistant organoceramic matrix that surpasses its homogeneous Data in parenthesis indicate conversion to carboxylic acid. analogs in terms of reactivity and ability to reuse. It is also superior to Influence of Catalyst and Temperature other supported TEMPO reagents, as it does not require activation Substrate Scope prior to use. SiliaCat TEMPO features include: Although KBr is not required for the reaction, it plays a significant role on SiliaCat TEMPO is efficient with different substrates and can be used kinetics of the reaction. The reaction can still go to completion without •Ease of handling and purification with a phase transfer agent (entry 4). When an electron-rich benzylic KBr but requires longer time (entry 2 vs 1) and/or more SiliaCat TEMPO •High Reactivity & TON alcohol cannot be oxidized successfully with NaOCl, conditions (entry 3). Oxidation can also be performed at room temperature without •No swelling, solvent independency, mechanical and thermal involving I in toluene, at room temperature [2] will lead to the desired KBr. 2 stability, and ease of scalability product (entry 8 vs 3, entries 9-10).

•Leach-resistant & reusable.

•Air stable, inert conditions not needed

SiliaCat TEMPO Properties KBr Temperature Time Conversion Entry SiliaCat TEMPO (mol %) o (equiv) ( C) (min) (%) Substrate SiliaCat TEMPO Time Conversion Organically modified silica made from hydrolysis and co- Entry 1 0.1 0.1 0 60 95 (R) (mol %) (min) (%) polycondensation 60 80 1 3-NO 0.4 90 100 2 0.1 0 0 2 210 100 2 4-NO 0.4 90 98 Loading: 0.8-0.9 mmol/g 2 3 0.2 0 0 105 96 3 4-MeO 0.4 90 36 Surface: 300-650 m2/g 60 76 a 4 4-MeO 0.4 60 79 Particle size: 60-250 microns 4 0.2 0 22 90 87 SiliaCat DPP-Pd 4 4-Cl 0.4 90 95 Pore size : 25-70 Å [R723-100] 6 3-phenyl-1-propanol 0.4 60 97

Influence of Solvents, pH and NaOCl 7 1-phenyl-1-propanol 0.4 180 95 b Catalytic Performance and Leaching 8 4-MeO 8.2 16h 99 b

Reactions can be carried out at pH 7.5 or pH 9.0 in DCM, water or EtOAc. 9 3-MeO 7.8 16h 96 b SiliaCat TEMPO was investigated in the Montanari-Anelli conditions. The amount of bleach used is important to limit over-oxidations to the 10 piperonyl alcohol 10 20h 100 The catalytic cycle involves regeneration of the oxidative species with corresponding carboxylic acid (entry 5). a 0.05 equiv of Aliquat 336 were used as phase transfer agent b o NaOCl (commercial bleach) in presence of KBr as co-catalyst to form Reaction conditions: I2(1.8eq), NaHCO3 (aq), pH 8, Toluene, 22 C - the stronger anion OBr . Conclusion

SiliaCat TEMPO is an effective oxidizing catalyst with unique SiliaCat TEMPO NaOCl Time Yield Entry (aq) Solvent pH advantages such as high activity, robustness, leach-resistant properties (mol %) (equiv) (min) (%) and selectivity toward the oxidation of alcohols to aldehydes and SiliaCat TEMPO Time (h) Conversion (%) Si (ppm) 1 0.2 2.5 DCM 9.0 60 98 ketones. 60 94 (mol %) 2 0.2 2.5 DCM 7.5 0.1 1 95 - 90 98 [1] A. Michaud, G. Gingras, M. Morin, F. Béland, R. Ciriminna, D.

0.02 2 96 - 60 87 Avini, M. Pagliaro, Org. Process Res. Dev.11 (2007) 766. 3 0.2 2.5 H2O 7.5 0.02 3 100 2 90 88

0.01 2 83 3 60 83 4 0.7 1.20 H O 9.0 [2] A. R. Miller, S. R. Hoerrner, Org. Lett. 5 (2003) 285. 0.01 3 95 1.6 2 150 89 a 0.01 4 97 1.5 60 60 (19) 5 0.8 5.0 H2O 9.0 a 18h 7 (89) 60 95 SiliaCat TEMPO can be used with as little 0.01 mol% to provide the 6 0.2 1.25 EtOAc 9.0 desired aldehyde in short reaction times. ICP analysis confirms that 90 96 the material is leach-resistant ([Si] ≤ 3ppm). a Data in parenthesis indicate conversion to carboxylic acid.