NMR Tech Talk: February 2015

Phenacetin (C10H13NO2), N-(4-Ethoxyphenyl) acetamide, is a drug that saw widespread application for nearly a century in many over-the-counter medications as a remedy for pain and fever.

The 82 MHz spectrum of a 6% (w/w; 0.5 M) solution of phenacetin in CDCl3 acquired using the Thermo Scientific picoSpin 80 NMR spectrometer.

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Quercetin (C15H10O7), 3,3',4',5-7-pentahydroxyflavone, is a flavonol, acts as a pigment in many fruits and vegetables, flowers, and leaves; the color of red onions and apples is caused by quercetin.

The 82 MHz spectrum of a 9.8% (w/w; 0.36 M) solution of Quercetin in protonated DMSO acquired using the picoSpin 80 NMR spectrometer. 

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γ-Butyrolactone (GBL) is a cyclic ester, a 5-membered heterocyclic ring referred to generally as a γ-lactone. Lactones are formed by cyclization of a hydroxy acid, where intramolecular esterification occurs between an alcohol (OH) group and carboxylic acid (COOH) group in the same molecule.

The 82 MHz spectrum of GBL diluted to 50% (v/v) in CDCl3 acquired using the picoSpin 80 NMR spectrometer shows two distinct spectral groups.

Based on signal area integration and multiplicity patterns, the signal at 4.31 ppm can be assigned as originating from excitation of protons on carbon atom C2; the adjacent ester oxygen atom (O1) causes these protons to shift to higher frequency than C3 or C4 protons. The triplet multiplicity arises from coupling to two neighboring protons on C3. Protons on C3 and C4 have an average chemical shift of 2.35 ppm making unambiguous assignment of multiplicities difficult. Protons on C4 are expected to shift to slightly higher frequency than C3 protons due to the proximity of the carbonyl carbon (C5), and should have triplet multiplicity arising from coupling to two C3 protons. Protons on C3, however, are coupled to both C2 and C4 protons, producing a pentet multiplicity pattern and should appear at lower frequency with respect to the C4 signal group.

GBL has several commercial and industrial applications; it is used as an intermediate chemical in the manufacture of pyrrolidines (cyclic amines used as building blocks in the synthesis of more complex compounds) and as a solvent in circuit board cleaning of electronics and high-end technologies. GBL is used in paint stripping, and found as a component in superglue and nail polish removers. It is used in the production of herbicides, as a processing aid in the production of pharmaceuticals, and generally used as a reagent and solvent in chemistry. GBL is also a prodrug of GHB (γ-hydroxybutanoic acid). A prodrug is a precursor chemical compound that can be converted to a drug through normal metabolic processes. Prodrug’s are often inactive or demonstrate less activity than the full strength drug, though occasionally possessing the ability to increase bioavailability of the drug. GBL is not pharmacologically active but is rapidly converted to GHB by lactamase found in the blood. GHB is considered a narcotic and thus is a controlled substance in many countries.

Spectral quality is foremost with picoSpin spectrometers, while also providing convenience, flexibility, portability, and reliability. The picoSpin™ 80 NMR spectrometer requires only 40 microliters of sample volume to fill the full flow path of the capillary cartridge allowing one to work with small sample volumes; an ideal design scenario for mass-limited samples and where reducing chemical waste is a concern. Small, liquid organic heterocyclic compounds such as GBL are easily evaluated as neat samples, or modestly diluted, to yield high-quality spectroscopic information. Analyzing less than 100 nanoliters of material in the spectrometer’s radio frequency coil, the picoSpin 80 quickly delivers both qualitative and quantitative high-resolution 82 MHz 1H spectra in just a handful of scans.

Chemical name: γ-Butyrolactone (GBL; gamma-butyrolactone)
Experimental conditions: 10 scans
Concentration: 50% (v / v) in CDCl3
CAS: 96-48-0
Field: 82 MHz
Nuclear testing: 1H
Applications: Solvents, forensics, bench analysis, QA / QC, productivity