NMR Spectrum of Phenacetin

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.

This spectrum is uncomplicated and easily interpreted, having four distinct functional groups populating its spectrum: an ethoxy (OCH₂CH₃), a phenyl (-Ph), an acetamide (NHC=O) and an acetyl group (O=CCH₃). The doublet of doublet signal pattern in the aromatic region (6.5 ppm - 7.5 ppm) is characteristic of para substitution on the aromatic ring. The large separation of the two doublets arises from asymmetry of the substituents, with protons nearest the acetamide group (on C₆,₈) shifting downfield (7.3 ppm). The acetamide signal (8.1 ppm) appears as a broad singlet due to relaxation dynamics of the attached N atom. The ethoxy group produces a classic ethyl triplet-quartet signal pattern at 1.4 ppm and 4.0 ppm, respectively, while the acetyl methyl protons appear as an uncouple singlet at 2.1 ppm.

Phenacetin is one of the first commercially produced synthetic pharmaceuticals and the first non-opioid analgesic; it was widely distributed in A.P.C. cold tablets since it was frequently mixed with aspirin and caffeine. This compound is representative of a class of acetanilide-based analogues known to have analgesic and antipyretic properties. Other compounds within this class are paracetamol (acetaminophen), lidocaine and highly potent opioid analgesic acetylfentanyl. Like the parent compound acetanilide, phenacetin is metabolized into paracetamol in the human body. Phenacetin was first withdrawn from market use in Canada in 1978 as it was found to be carcinogenic and cause kidney damage, with most countries withdrawing its use in over-the-counter medications in the subsequent years. Drugs utilizing phenacetin were reformulated with paracetamol, which was found to have similar pain and fever reducing properties but is non-carcinogenic. Currently phenacetin is has no legal use, though is used illegally in some countries as a cutting agent for cocaine.

High-resolution spectroscopy in a true bench-top instrument like the picoSpin™ 80 ¹H NMR spectrometer is at the forefront of modern spectrometer design. The novel approach of a flow-path capillary cartridge probe coupled with modern rare earth magnetic materials in a pole-gap design yields a high-performance, high-resolution results spectroscopy in a compact and mobile instrument. Liquid samples are injected into the capillary probe as dilute solutions in protonated or deuterated solvents, or as neat liquids, with as little as 40 microliters of sample volume needed. By design, sample-to-sample shimming is not required and the software lock makes optional the need for deuterated solvents. Compact, affordable bench-top NMR spectroscopy has never been easier.

Chemical name: Phenacetin (N- (4-Ethoxyphenyl) acetamide)
Concentration: 6% (w / w; 0.5 M) in CDCl3
CAS: 62-44-2
Field: 82 MHz
Nuclear testing: ¹H
Applications: Pharmaceuticals, forensics, bench analysis, productivity

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