Question

After luminol is synthesized/isolated, it was re- dissolved in an aqueous NaOH solution. Explain why amide protons are removed under the given basic conditions, whereas the amine protons are not removed from the molecule.

Answer 1

The Proton Chemical Shift Scale

  Experimentally measured proton chemical shifts are referenced to the ¹H signal of tetramethylsilane (Me₄Si). For NMR studies in aqueous solution, where Me₄Si is not sufficiently soluble, the reference signal usually used is DSS (Me₃Si-CH₂CH₂-SO₃^-Na⁺, Tiers, J. Org. Chem. 1961, 26, 2097). For aqueous solution of cationic substrates (e.g., amino acids) where there may be interactions between the anionic reference compound and the substrates, an alternatice reference standard, DSA (Me₃Si-CH₂CH₂-NH₃⁺ CF₃CO₂^-, Nowick Org. Lett. 2003, 5, 3511) has been suggested.

  Proton chemical shifts cover a range of over 30 ppm, but the vast majority appear in the region ? 0-10 ppm, where the origin is the chemical shift of tetramethylsilane.

  

  In the original continuous wave (CW) method of measuring NMR spectra, the magnetic field was scanned from left to right, from low to high values. We thus refer to signals on the right as upfield or shielded and signals to the left as downfield or deshielded. Later spectrometers gained the capability of scanning frequency, which then had to decrease from left to right during the scan, hence the "backwards" nature of NMR scales. ? units are defined as follows:

  

  Chemical shifts of all nuclei should be reported using ? values, with frequency and ? increasing from right to left. Many early papers on proton and multinuclear NMR used the opposite convention (not to mention other references) - in particular the ? scale was used in the early days: ? = 10 - ?. Coupling constants are field independent, and should always be specified in Hz.IUPAC Recommendations.

  The chemical shifts of protons on carbon in organic molecules fall in several distinct regions, depending on the nature of adjacent carbon atoms, and the substituents on those carbons. The scale below should be used only as a rough guideline, since there are many examples that fall outside of the indicated ranges. To a first approximation, protons attached to sp³ and sp carbons appear at 0-5 ppm, whereas those on sp² carbons appear at 5-10 ppm.

  

  Within these ranges, for a given type of C-H bond (sp³, sp² or sp) the chemical shift is strongly affected by the presence of electronegative substituents as can be seen in the methyl shifts summarized below, which range from ? -2 for MeLi to ? 4 for MeF.

  

  The ¹H chemical shifts of protons attached to heteroatoms (H-X) show a very wide chemical shift range, with no obvious correlation to the electronegativity of X or the acidity of HX.

  

1. Electronegativity. Proton shifts move downfield when electronegative substituents are attached to the same or an adjacent carbon (see Curphy-Morrison chemical shift table). Alkyl groups behave as if they were weakly electron withdrawing, although this is probably an anisotropy effect.

  

  The chemical shifts of protons attached to sp² hybridized carbons also reflect charges within the ? system (approximately 10 ppm/unit negative or positive charge).

  

  Even without formal charges, resonance interactions can lead to substantial chemical shift changes due to ? polarization.

  

  This is especially useful in the interpretation of the NMR chemical shift of protons in aromatic systems. The protons ortho and para to electron donating and electron withdrawing substituents show distinct upfield and downfield shifts.

  

  2. Lone Pair Interactions. When lone pairs on nitrogen or oxygen are anti to a C-H bond, the proton is shifted upfield (n --> ?* interactions). There is thus a strong conformational dependence of chemical shifts of protons ? to heteroatoms. This interaction is one of the reasons that Curphy-Morrison chemical shift calculations work poorly when multiple O or N substituents are attached to one carbon. This effect is also present in ¹³C chemical shifts. C-H bonds anti to lone pairs also show Bohlmann bands in the IR spectra, as a result of weakening of the C-H bond by hyperconjugation. For example, the ? = 180