Efficient, scalable and economical preparation of tris(deuterium)‐ and ¹³C‐labelled N‐methyl‐N‐nitroso‐p‐toluenesulfonamide (Diazald®) and their conversion to labelled diazomethane

Abstract

A method for the preparation of multi-gramme quantities of N-methyl-d3-N-nitroso-p-toluenesulfonamide (Diazald-d3) and N-methyl-(13)C-N-nitroso-p-toluenesulfonamide (Diazald-(13)C) and their conversion to diazomethane-d2 and diazomethane-(13) C, respectively, is presented. This approach uses robust and reliable chemistry, and critically, employs readily commercially available and inexpensive methanol as the label source. Several reactions of labelled diazomethane are also reported, including alkene cyclopropanation, phenol methylation and α-diazoketone formation, as well as deuterium scrambling in the preparation of diazomethane-d2 and subsequent methyl esterification of benzoic acid.

Trimethylation Enhancement Using 13C-Diazomethane (13C-TrEnDi): Increased Sensitivity and Selectivity of Phosphatidylethanolamine, Phosphatidylcholine, and Phosphatidylserine Lipids Derived from Complex Biological Samples

“…This issue was overcome through the synthesis of 13 C-labeled diazomethane 25 for use in TrEnDi derivatization (Scheme 1). Derivatization with this reagent results in a PIS of m/z 202.1, exclusive to PE species, and a PIS of m/z 199.1 for PC and SM species (Figure 1).…”

“…PE­(16:0/18:1­(9Z)), PC­(16:0/18:1­(9Z)), PE­(8:0/8:0), PS­(8:0/8:0), and PC­(5:0/5:0) were synthesized by and obtained from Avanti Polar Lipids Inc. (Alabaster, Alabama, USA). N -(Methyl- 13 C )- N -nitroso- p -toluenesulfonamide was readily prepared from 13 C -methanol (Cambridge Isotope Laboratories, Cambridge, Massachusetts, USA), an inexpensive and widely available 13 C label source, according to the procedure reported by Shields and Manthorpe …”

The Deuterated “Magic Methyl” Group: A Guide to Site‐Selective Trideuteromethyl Incorporation and Labeling by Using CD3Reagents

“…Analogously to methyl tosylate, CD 3 OTs was recently employed as an electrophilic trideuteromethylation reagent that can be easily prepared from CD 3 OD and TsCl in one step. [87] In 2018, Osaka reported the transformation of ArX (X=I, Br, Cl, OTf) into ArCD 3 by reductive coupling with CD 3 OTs using Ni/Co dual catalysis (Scheme 22 a). [50] The Co catalyst plays a crucial role in transmethylation.…”

Frontispiece: The Deuterated “Magic Methyl” Group: A Guide to Site‐Selective Trideuteromethyl Incorporation and Labeling by Using CD3 Reagents

“…Analogously to methyl tosylate, CD 3 OTs was recently employed as an electrophilic trideuteromethylation reagent that can be easily prepared from CD 3 OD and TsCl in one step. [87] In 2018, Osaka reported the transformation of ArX (X=I, Br, Cl, OTf) into ArCD 3 by reductive coupling with CD 3 OTs using Ni/Co dual catalysis (Scheme 22a). [50] The Co catalyst plays a crucial role in transmethylation.…”