1H NMR Evidence for High Barriers to Amino Group Rotation in 4-Aminopyrimidines, Including Thiamin, at Low pH in Water

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The 1H NMR spectrum of thiamin (1), 4-aminopyrimidine (2), 4-ammc-5-(methoxymethyl)-2-methylpyrimidine (3), and thiothiamin (4) was recorded at a variety of concentrations, temperatures, and pH's in 80:20 (v/v) H2O—2H2O employing correlation spectroscopy and Redfield 2-1-4 sequences at 360 and 500 MHz. At pH's 1.5 to 3.0 units below the pK for N1 protonation, two amino hydrogen resonances were observed to persist at temperatures below about 10 °C for 1, 26 °C for 2, 40 °C for 3, and 15 °C for 4, indicative of hindered amino group rotation under these conditions. The concentration and temperature dependence of the behavior of the two NH resonances at low pH suggest that the increased barrier is not due to intermolecular interactions but simply to the favorable resonance interaction between the amino group nitrogen lone pair and the pyrimidine ring once the latter is N1 protonated. The barrier to amino group rotation in N1′-protonated thiamin was estimated to be 14.6 kcal/mol at pH 1.56, 12 °C, in 1 M KCl solution.

Original languageEnglish (US)
Pages (from-to)2748-2753
Number of pages6
JournalJournal of Organic Chemistry
Issue number14
Publication statusPublished - Jan 1 1982


All Science Journal Classification (ASJC) codes

  • Organic Chemistry

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