Specificity of 15N NMR chemical shifts to the nature of substituents and tautomerism in substituted pyridine N-oxides

Structural Chemistry, Feb 2013

1H, 13C, and 15N NMR chemical shifts have been measured for 2-aminopyridine N-oxide (1), its eleven derivatives (2–10, 13, 14), and 3-Cl and 3-Br substituted 4-nitropyridine N-oxides (11, 12). δ(15N) of pyridine ring nitrogen in 2-acetylaminopyridine N-oxides are 5.9–11.5 ppm deshielded from those in 2-aminopyridine N-oxides. When amino and acetylamino substituents are in 4-position, δ(15N) of ring nitrogen is 21.3 ppm deshielded in the acetylated derivative. The strong resonance interaction between 2-amino and 5-nitro groups reflects in the decrease of amino nitrogen shielding about 5.3–17.9 ppm. Also, 1H and 13C NMR spectral data are in agreement with 15N NMR results reflected as deshielded amino protons and carbons C-2 and C-5. The pyridine nitrogen chemical shift in all amino- and acetylamino derivatives vary between −101.2 and −126.7 ppm, which has been connected with the tautomeric balance in our earlier studies.

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Specificity of 15N NMR chemical shifts to the nature of substituents and tautomerism in substituted pyridine N-oxides

Aniela Puszko 0 1 Katri Laihia 0 1 Erkki Kolehmainen 0 1 Zofia Talik 0 1 Z. Talik: Deceased. 0 1 0 K. Laihia E. Kolehmainen Department of Chemistry, University of Jyvaskyla , FI-40014 Jyvaskyla, Finland 1 A. Puszko (&) Z. Talik Department of Bioorganic Chemistry, Faculty of Industry and Economics, University of Economics , 53-345 Wrocaw, Poland 1H, 13C, and 15N NMR chemical shifts have been measured for 2-aminopyridine N-oxide (1), its eleven derivatives (2-10, 13, 14), and 3-Cl and 3-Br substituted 4-nitropyridine N-oxides (11, 12). d(15N) of pyridine ring nitrogen in 2-acetylaminopyridine N-oxides are 5.9-11.5 ppm deshielded from those in 2-aminopyridine N-oxides. When amino and acetylamino substituents are in 4-position, d(15N) of ring nitrogen is 21.3 ppm deshielded in the acetylated derivative. The strong resonance interaction between 2-amino and 5-nitro groups reflects in the decrease of amino nitrogen shielding about 5.3-17.9 ppm. Also, 1H and 13C NMR spectral data are in agreement with 15N NMR results reflected as deshielded amino protons and carbons C-2 and C-5. The pyridine nitrogen chemical shift in all amino- and acetylamino derivatives vary between -101.2 and -126.7 ppm, which has been connected with the tautomeric balance in our earlier studies. Introduction 15N isotope is the most sensitive NMR nucleus to the effect of a substituent introduced to pyridine N-oxide (2- and 4-amino, 2- and 4-acetylamino, methyl group in different positions together with 2-amino and/or 2-acetylamino, 5-nitro with 2-amino, 4-nitro together with 3-chloro and 3-bromo e.g.). Pyridine N-oxides possess an NO-moiety, a dual resonance functionality, that can act as both a p-electron donor and a p-electron acceptor [1]. Acceptors in the ring decrease and donors increase the shielding of 15N. A linear relationship has been observed between the substituent chemical shifts of 15N and 13C for the related substituted benzenes. Only few research reports on 15N and 14N NMR studies of aminopyridine N-oxides are found in the literature [25]. In this paper, we present our studies regarding the possible tautomerism in amino and acetylaminopyridine N-oxides because this problem has not yet been unambiguously solved. Another interest lies in the 5-nitro-substituted compounds (10, 13, 14), where the electron lone pair of amino moiety is involved in the p-electron conjugation with the aromatic ring the nitro group acting as an electron acceptor. Recently, 2-amino-5-nitropyridine derivatives have been shown to be very interesting owing to their promising nonlinear optical properties as these molecules possess high hyperpolarizability and highly delocalised p-electron system for reason that acceptor and donor group are situated in para-position to each other [6]. Experimental 2-Aminopyridine N-oxide and its 3- and 5-methyl derivatives were obtained by protecting the primary amino group by acetylation during the oxidation of ring nitrogen. Otherwise, oxidation would have transformed aminopyridines into nitropyridines [715]. In hydrolysis, acetylamino derivatives of pyridine N-oxide gave the corresponding amino compounds [7]. 2-Amino- and 2-acetylaminopyridine N-oxides as well as their 3-, 4-, 5-, and 6-methyl derivatives are reported in literature [8, 9], but their synthesis were greatly improved [14] compared to the earlier reported methods [813]. The modified synthesis of 2-acetylaminopyridine N-oxides (2, 4) and 4-, 5-, and 6-methyl-(2-acetylaminopyridine-Noxides) (7, 8, 9) [810, 13] has been presented previously [14]. By modification of methods by Brown and Adam et al. [9, 10], a remarkable shortening in reaction time (9 to 2 h) was achieved by substituting acetic acid by acetic anhydride in the reaction. The syntheses of 2-amino- (1), 4-amino- (3), 2-amino-3methyl- (5), 2-amino-5-methylpyridine N-oxide (6) have also been reported earlier [16]. These compounds were obtained by hydrolysis of the corresponding acetylaminopyridine N-oxides [13]. By Herzs hydrolysis method [13] with 50 % H2SO4 instead of 10 % NaOH decreases, the reaction time varied from 5 to 1 h [9, 10]. The syntheses of 2-amino-5-nitro- (10), 2-amino-5nitro-3-methyl- (13) and 2-amino-5-nitro-6-methylpyridine N-oxides (14) have been presented previously [16, 17]. These compounds were obtained in rearrangement reaction of the corresponding nitraminopyridine N-oxides [16, 17]. 3-Chloro- (11) and 3-bromo-4-nitropyridine N-oxides (12) were prepared by oxidation of 3-chloro- and 3-bromopyridine by 30 % H2O2 in the presence of acetic anhydride followed by nitration of the crude products after the excess acid was removed [18]. The modification of this synthesis in comparison with earlier applied methods [7] consists an improvement of N-oxidation (using acetic anhydride instead of acetic acid) and separation of final product from reaction mixture (using 25 % NH4OH and NH4HCO3 instead of NaOH) giving the pure product due to low temperature during the neutralization proces (...truncated)


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Aniela Puszko, Katri Laihia, Erkki Kolehmainen, Zofia Talik. Specificity of 15N NMR chemical shifts to the nature of substituents and tautomerism in substituted pyridine N-oxides, Structural Chemistry, 2013, pp. 333-337, Volume 24, Issue 1, DOI: 10.1007/s11224-012-0069-0