Oxidation of 3-Phenyl-1-Propanol using a Catalytic Oxoammonium Salt; 3-Phenylpropanal
SyntheticPage 706
DOI:
10.1039/SP706
Submitted Nov 29, 2013, published Nov 30, 2013
Chemicals Used
3-Phenyl-1-propanol (98%, Sigma-Aldrich)
4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (Prepared In-House, See Comment 1)
Chlorox® Bleach (6% w.w. NaOCl)
Dichloromethane (≥99.5%, ACS Reagent Grade, Sigma-Aldrich)
Procedure
To a 250 mL round bottom flask equipped with a stir bar, was added 3-phenylpropan-1-ol (4.09 g, 30 mmol, 1 equiv) and DCM (75 mL, 0.4 M solution of alcohol). The oxoammonium salt (1.08 g, 6 mmol, 0.2 equiv2) was added to the solution. While stirring, commercial bleach (37.5 mL, 30 mmol, 1.0 equiv3) was added all at once where the solution turned from yellow to bright red color. The solution was allowed to stir vigorously at room temperature for 60 min and monitor by GC-MS to assure reaction completion. Once the reaction is complete, the solution was transferred to a separatory funnel and diluted with 50 mL of deionized water and extract with DCM (3 X 50 mL). The combined organic layers were washed with 100 mL of brine and dried over sodium sulfate. The solvent was removed in vacuo by rotary evaporation, affording the crude aldehyde.
The crude alcohol was then adhered to silica gel by mixing it with 1.5 weight equivalents silica gel (relative to the theoretical yield, in this case ≈ 6 g), dissolving it in CH
2Cl
2 (50 mL) and removing the solvent
in vacuo by rotary evaporation. A plug of silica was then assembled. This was done by adding 3-4 weight equivalents of silica (again relative to the theoretical yield) to a 150 mL coarse-porosity fritted glass funnel. An appropriately sized piece of filter paper relative to the size of the funnel was used to the top of the dry silica gel layer and this layer was pre-wet with hexanes. The dry packed material was gentle added evenly atop the filter paper. Another piece of appropriately sized filter paper was added atop this layer. The desired alcohol was eluted off the plug
via a 95:5 by volume mixture of Hex:EtOAc (3 column volumes). The solvent was removed
in vacuo by rotary evaporation to afford the pure aldehyde (2.21 g, 55%)
4 as a clear, colorless oil.
Author's Comments
1. While this oxoammonium salt is available commercially from Sigma Aldrich, we prefer to prepare in-house than to purchase it. A procedure for its preparation from inexpensive commercially available 4-amino-2,2,6,6-tetramethylpiperidine can be found in the other references section below. A Chemspider Synthetic Page for its preparation is forthcoming.
2. While we suggest that 20 mol% of the oxidant be employed, as low as 10 mol% can be used. However, lower loadings gave inconsistent results. If lower loadings are used, reaction monitoring is essential. Additional bleach and the oxoammonium salt may be necessary to ensure reaction completion.
3. It is recommended that fresh, unopened bleach be used. Opened bottles may be used, but note that the oxidizing capacity of bleach diminishes over time when exposed to atmospheric conditions (via quenching of the hypochlorite ion). If older/opened bottles are employed, reaction monitoring is essential. More bleach and the oxoammonium salt may be needed to reach reaction completion.
4. While this yield is somewhat diminished, other substrates gave far better yield using identical oxidation conditions. We suggest that it relates to the propensity for over oxidation (to its corresponding carboxylic acid) which is a function of the aldehyde's hydration potential. Aromatic aldehydes (benzaldehyde derivatives) give enhanced yields under these conditions likely because they do not form hydrates appreciably. For more information on this concept see Other References 2.
Data
1H NMR (CDCl3, 400 MHz) d ppm 2.79 (t, J=8.00 Hz, 2 H) 2.97 (t, J=7.60 Hz, 2 H) 7.17 - 7.24 (m, 3 H) 7.30 (apparent triplet, J=7.00 Hz, 2 H) 9.83 (t, J=1.46 Hz, 1 H)
13C NMR (CDCl3, 100 MHz) d ppm 28.38 (CH2) 45.54 (CH2) 126.57 (CH) 128.56 (CH) 128.87 (CH) 140.61 (C) 201.80 (C)
GC-MS (EI) 134 ([M]+, 61%) 133 ([M-1]+, 10%) 105 (33%) 103 (16%) 92 (72%) 91 (100%) 78 (47%) 65 (16%)
Lead Reference
Kelly, C. B.; Mercadante, M. A.; Wiles, R. W.; Leadbeater, N. E. Org. Lett., 2013, 15, 2222
Other References
1. Mercadante, M. A.; Kelly, C. B.; Bobbitt, J. M.; Tilley, L. J.; Leadbeater N. E. Nat. Protoc. 2013, 8, 666
2. Qiu, J. C.; Pradhan, P. P.; Blanck, N. B.; Bobbitt, J. M.; Bailey, W. F. Org. Lett., 2012, 14, 350.
Supplementary Information
e.g. Actual NMR spectra (as images or jdx files for interactive spectra), photographs of apparatus, TLC’s or crystals or videos. Please contact the ChemSpider team (ChemSpider-at-rsc.org) for help with this.
1H NMR (phenylpropanal.jpg)
13C NMR (phenylpropanal C13.jpg)
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Keywords: alcohols, aldehydes, Green Chemistry, Organic Oxidants, oxidation, Oxoammonium Salts
