NMR Spectrum of Propranolol Hydrochloride
(±)-Propranolol hydrochloride (C16H21NO2 · HCl), a nonselective beta-blocker, is representative of a class of drugs that target the beta receptor. It is prescribed medication for treatment of hypertension, severe headaches, and cardiac related dysrhythmia and ischemia.
The 1H NMR spectrum of a 11.2% (w/w; 420 mM) solution of propranolol in protonated DMSO was measured at 82 MHz using the Thermo Scientific™ picoSpin™ 80 spectrometer.
The solvent, DMSO, produces a strong resonance at 2.50 ppm, which is used as a chemical shift reference. Only the downfield 13C satellite signal (3.33 ppm; 0.55% intensity) overlaps analyte signals. Despite the complexity of the spectrum, propranolol can be viewed as containing 3 spin systems: a fused-ring aromatic (C10H7O), an aliphatic chain (-CHn-) and an isopropyl (i-Pr) group. Hydroxyl (OH) and the secondary amine (NH) also produce distinct signals in the spectrum.
Chemical shift assignment of the naphthyloxy proton resonances is aided by peak integration. Anisotropic effects and ring substitution cause the aromatic protons to shift in the region from 6.7 to 8.3 ppm. The roughly equal intensity multiplets assigned to protons at C9, C6 and C2 show a 1:1:1 integral ratio and anticipated chemical shifts of 8.25 ppm (1H), 7.8 ppm (1H) and 6.9 ppm (1H), respectively. The doublet of doublet multiplicity arises from vicinal 3J (6 Hz) and long-range 4J (3 Hz) coupling across the π system. The multiplicity of remaining ring protons, C3,4,7,8, appearing between 7.25-7.6 ppm, is obscured by signal overlap, making individual assignment difficult. Peak integration, however, reveals four protons (4H) contribute to signal intensity.
The isopropyl group gives rise to a doublet methyl signal at 1.25 ppm (C18,19; 6H), due to coupling to a single methine proton (CH), and an broad multiplet (~3.2 ppm; C17) from the same. The aliphatic chain protons (C12-C13-C15) are assigned to resonances at 4.13 ppm (2H), 4.39 ppm (1H) and 3.16 ppm (2H), respectively, based on scalar coupling, peak integration, and chemical shift. The hydroxyl proton (OH) assignment to the doublet resonance at 6 ppm is based on peak integration (1H) and multiplicity, having one neighboring proton on C13. The secondary amine proton (NH) is assigned the broad absorption centered at 9 ppm. Severe signal broadening suggests slow or intermediate dynamic exchange, as well as expected quadrupolar interaction.
At 82 MHz the picoSpin 80 1H NMR spectrometer offers the highest field strength in a compact benchtop instrument, delivering chemical shift dispersion and resolution unmatched by other desktop NMR systems. These features facilitate spectral assignment of complex molecular structures by producing qualitative spectral quantities. Shift dispersion and high-resolution means one can discriminate closely spaced proton resonances while also extracting scalar coupling frequencies. Peak integration yields quantitative information, further strengthening shift assignments. picoSpin spectrometers offer personal convenience without waiting for core facility resources while also providing structure selectivity and high discriminating power in a compact benchtop instrument.
Chemical name: (±) -Propranolol hydrochloride; (±) -1-Isopropylamino-3- (1-naphthyloxy) -2-propanol hydrochloride
Concentration: 11.2% (w / w; 0.42 M) in DMSO
Field: 82 MHz
Nuclear testing: 1H
Applications: Pharmaceuticals, R & D, Bench Analysis
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