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. 2021 Dec 30;7(1):293-298.
doi: 10.1021/acsomega.1c04679. eCollection 2022 Jan 11.

TfNN15N: A γ-15N-Labeled Diazo-Transfer Reagent for the Synthesis of β-15N-Labeled Azides

Hyeok-Jun Kwon  1 , Sungduk Gwak  1 , Jun Young Park  1   2 , Minhaeng Cho  1   2 , Hogyu Han  1
Affiliations

TfNN15N: A γ-15N-Labeled Diazo-Transfer Reagent for the Synthesis of β-15N-Labeled Azides

Hyeok-Jun Kwon et al. ACS Omega. .

Abstract

Azides are infrared (IR) probes that are important for structure and dynamics studies of proteins. However, they often display complex IR spectra owing to Fermi resonances and multiple conformers. Isotopic substitution of azides weakens the Fermi resonance, allowing more accurate IR spectral analysis. Site-specifically 15N-labeled aromatic azides, but not aliphatic azides, are synthesized through nitrosation. Both 15N-labeled aromatic and aliphatic azides are synthesized through nucleophilic substitution or diazo-transfer reaction but as an isotopomeric mixture. We present the synthesis of TfNN15N, a γ-15N-labeled diazo-transfer reagent, and its use to prepare β-15N-labeled aliphatic as well as aromatic azides.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. (a–d) Syntheses of Site-Specifically 15N-Labeled Azides
Scheme 2
Scheme 2. Synthesis of TfNN15N 1
Figure 1
Figure 1
IR spectra of TfNN15N 1 and TfNNN 1′ in CH2Cl2 at 20 °C.
Scheme 3
Scheme 3. Syntheses of Azides 3 by Diazo-Transfer Reactions of Amines 2 with TfNN15N 1
Figure 2
Figure 2
1H NMR spectra (500 MHz, CDCl3) of AlaN15NN 3a and AlaNNN 3a′ in the β-proton region: 3a, δ 3.73 (ddd, J = 12.4, 5.1, 3.6 Hz, 1H), 3.53 (ddd, J = 12.3, 6.3, 3.8 Hz, 1H); 3a′, δ 3.72 (dd, J = 12.3, 4.8 Hz, 1H), 3.54 (dd, J = 12.3, 6.3 Hz, 1H).
Figure 3
Figure 3
IR spectra of AlaN15NN 3a and AlaNNN 3a′ in DMF at 20 °C.
See this image and copyright information in PMC

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