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Synthesis of 15 N‐labelled 3,5‐dimethylpyridine
Author(s) -
Schubert Mario,
Limbach HansHeinrich,
Elguero José
Publication year - 2019
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3807
Subject(s) - chemistry , chemical shift , pyridine , protonation , ether , nuclear magnetic resonance spectroscopy , chemical synthesis , alkoxy group , stereochemistry , medicinal chemistry , organic chemistry , alkyl , ion , biochemistry , in vitro
15 N‐labelled pyridines are liquid‐ and solid‐state nuclear magnetic resonance (NMR) probes for chemical and biological environments because their 15 N chemical shifts are sensitive to hydrogen‐bond and protonation states. By variation of the type and number of substituents, different target pyridines can be synthesized exhibiting different p K a values and molecular volumes. Various synthetic routes have been described in the literature, starting from different precursors or modification of other 15 N‐labelled pyridines. In this work, we have explored the synthesis of 15 N 15 N‐labelled pyridines using a two‐step process via the synthesis of alkoxy‐3,4‐dihydro‐2 H ‐pyran as precursor exhibiting already the desired pyridine substitution pattern. As an example, we have synthesized 3,5‐dimethylpyridine‐ 15 N (lutidine‐ 15 N) as demonstrated by 15 N‐NMR spectroscopy. That synthesis starts from methacrolein, propenyl ether, and 15 N‐labelled NH 4 Cl as nitrogen source.