Acide (isobutyl-4 phenyl)-2 propionique
Ibuprofen is the active ingredient in a number of over the counter pain relievers, e.g. Advil, Motrin, and Nuprin. It is one of the top-ten drugs sold worldwide, and, although it has been shown that only the S enantiomer has the desired biological activity, it is currently sold as the racemate. Our synthesis of the racemate, begins with reaction of 4-isobutylacetophenone with the sulfur ylide produced by deprotonation of trimethylsulfonium iodide to yield an epoxide. (You should look this reaction up in an advanced organic text, e.g. the one by Jerry March.) In the JOC article listed above they found that the epoxide could be converted to Ibuprofen by reduction to the alcohol using H2/Pd followed by oxidation of the resulting alcohol to the acid using KMnO4. We found that BF3Et2O catalyzed rearrangement of the epoxide to an aldehyde worked well. Some preliminary attempts at oxidizing this aldehyde to Ibuprofen have been explored.
The simplified 2-dimensional molecular structure of the common NSAID (non-steroidal anti-inflammatory drug) Ibuprofen is shown below, along with the 1-Dimensional proton (1H) NMR spectrum of this compound. They hydrogen atoms are colored, to correspond with the peaks in the NMR spectrum.
The protons that are different (chemically speaking) have different NMR frequencies because the chemical environment causes the local magnetic field for that nucleus to be unique. The "PPM" axis is used to report frequency differences that are scaled by the magnetic field strength. This allows the peak positions to be compared for spectra acquired at various magnetic field strengths, without having to do any conversions. Zero, on this PPM axis, is the frequency position (orchemical shift) of a compound called Tetramethyl Silane or TMS.
The NMR signals from the various chemically unique protons appear not as single peaks, but as multiplets of peaks. This is because the spins of the hydrogen nuclei bonded to neighboring carbon atoms perturb the energy of the NMR signals. This effect is often called "J-coupling," "spin-spin splitting," or "scalar coupling." For example, the CH hydrogen (shown in green) is affected by six equivalent CH3 (red) hydrogen nuclei, and two equivalent (dark blue) CH2 hydrogens. Because there are eight hydrogen atoms on the neighboring carbon atoms, the NMR signal from the (green) CH is split into 9 different individual peaks (or a nonet). This follows the so-called "n+1" rule, which is over-simplified, but often taught to beginning students learning NMR spectroscopy. The (purple) CH that is adjacent to the (cyan) CH3 group appears as 4 peaks (or a quartet) because of the 3 hydrogens on the neighboring carbon. Click on each peak above to see an expanded view of the NMR signal.