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Oxidation of 3-(4-methoxyphenyl)prop-2-yn-1-ol by an Oxoammonium Salt; 3-(4-Methoxyphenyl)propiolaldehyde 

SyntheticPage 583
DOI: 10.1039/SP583
Submitted Dec 22, 2012, published Dec 28, 2012
Christopher Kelly (christopher.b.kelly@uconn.edu)
A contribution from Leadbeater Group
Reaction Scheme: <IMG src="/images/empty.gif">Oxidation of <SPAN id=csm1356709608564 class=csm-chemical-name title=3-(4-methoxyphenyl)prop-2-yn-1-ol grpid="1">3-(4-methoxyphenyl)prop-2-yn-1-ol</SPAN> by an Oxoammonium Salt<IMG src="/images/empty.gif">

Chemicals Used

4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (Prepared In-House, See Comment 1) 
3-(4-methoxyphenyl)prop-2-yn-1-ol (Prepared in house, see Synthetic Page 507)
Dichloromethane (≥99.5%, ACS Reagent Grade, Sigma-Aldrich) 
Silica Gel (Dynamic Adsorbants Inc. Flash Silica Gel, 60Å porosity, 32-63 µm)

Procedure

To a 500 mL flask equipped with stirbar was added the 3-(4-methoxyphenyl)prop-2-yn-1-ol (2.75 g, 0.01696 mol, 1 equiv) and DCM (170 mL, 0.1M in the alcohol). After mixing for a few minutes, 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate1 (5.34 g, 0.01780 mol, 1.05 equiv.) was added followed by 2.75 g of SiO2 (1 mass equiv. to substrate)2. The flask was sealed with a rubber septa and the mixture was allowed to stir vigerously3 for 24 hours at room temperature. Upon reaction completion4 (confirmed by GC/MS analysis), the slurry was filtered solvent filtered through a coarse porosity fritted funnel. The solids were rinsed thoroughly with CH2Cl2 (≈ 300 mL). The filtrate was then adhered to silica gel by mixing it with 1.5 weight equivalents silica gel (relative to the theoretical yield, in this case 4.08 g) and removing the solvent in vacuo by rotary evaporation. A plug of silica was then assembled (A diagram of this apparatus is in the Data Files). This was done by adding 3-4 weight equivalents of silica (again relative to the theoretical yield) to a 60 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 plug was eluted with a 9:1 by volume mixture of Hex:EtOAc (2-3 column volumes). The solvent was removed in vacuo by rotary evaporation to afford the pure aldehyde (1.72 g, 63%) as a tan solid.

Author's Comments

  1. While this oxoammonium salt is available commercially, is far more cost-effective 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 lead reference and a Chemspider Synthetic Page for its preparation is forthcoming.
  2. Bobbitt has shown that the presence of silica gel has a marked increase in the rate of the reaction which can be attributed the relative surface concentration of the reactants. While more important for more difficult to oxidize alcohols (primary aliphatic), SiO2 speeds up these oxidations in general. As more silica is added the reaction proceeds faster, (i.e. two weight equivalents proceeds faster than the one outlined in this procedure) however stirring becomes increasingly difficult. Therefore, for most applications, one weight equivalent is sufficient. For more information see Bobbitt, J. M. J. Org. Chem. 1998, 63, 9367.
  3. Failure to stir at an adequate rate leads to extended reaction times as the reaction is heterogeneous. Solubility of the oxoammonium salt is quite low in DCM (0.09 g in 100 mL).
  4. These reactions are very colorimetric in nature. At the beginning of the reaction, the slurry will be bright light yellow (from the oxoammonium salt). As the reaction progresses the yellow color diminishes ultimately until the slurry is completely white (from the SiO2 and the spent oxidant), the hydroxyamine tetrafluoroborate salt. This white color typically indicates reaction completion but some form of spectroscopy should be used to formally identify reaction completion.

Data

1H NMR (CDCl3, 400 MHz) δ ppm 3.83 (s, 3 H) 6.89 (d, J = 8.80 Hz, 2 H) 7.54 (d, J = 8.80 Hz, 2 H) 9.37 (s, 1 H)

 13C NMR (CDCl3, 100 MHz) δ ppm 55.7 (CH3) 89.0 (C) 96.8 (C) 111.3 (C) 114.7 (CH) 135.6 (CH) 162.4 (C) 176.9 (CH) 

GC-MS (EI) 161 ([M]+2, 11%), 160 ([M]+, 100%), 159 (59%), 144 (13%), 132 (46%), 117 (34%), 116 (11%), 89 (44%), 88 (11%), 63 (20%), 62 (16%), 44 (10%), 40 (36%).

 HRMS (ESI+) calcd for C9H9F3O2  [M + H]+ 161.0603, found: 161.0604

Lead Reference

Kelly, C. B; Mercadante, M. A.; Hamlin, T. A.; Fletcher, M. H.; Leadbeater, N. E. J. Org. Chem., 2012, 77, 8131.

Other References

Bobbitt, J. M. J. Org. Chem. 1998, 63, 9367.
Bobbitt, J. M.; Bruckner, C.; Merbouh, N. Organic Reactions 2010, 74, 103.
 

Supplementary Information

Plug Diagram (Plug Apperatus.jpg)
1H NMR (HNMR.jpg)
13C NMR (13C NMR.jpg)

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Keywords: aldehydes, alkynes, Organic Oxidants, oxidation, Oxoammonium Salts