Nucleophilic aromatic substitution by [18F]fluoride at substituted 2-nitropyridines was written by Malik, Noeen;Solbach, Christoph;Voelter, Wolfgang;Machulla, Hans-Juergen. And the article was included in Journal of Radioanalytical and Nuclear Chemistry in 2010.Quality Control of 3-Hydroxy-6-methyl-2-nitropyridine This article mentions the following:
For the radiofluorination of benzenes and benzene derivatives, the electrophilic reaction with [18F]F2 is a very common route. Yet, aromatic nucleophilic substitution (SNAr) by n.c.a [18F]fluoride, which can be produced efficiently in high amounts, has been considered to be very desirable. However, to facilitate 18F-labeling via SNAr at an electron rich aromatic system, an appropriate leaving group must be present together with an auxiliary group in ortho or para position to the leaving group. An interesting alternative for the auxiliary group is the heteroatom of a heteroaromatic system, for which pyridine is a leading example. Dolci et al. (J Label Compd Radiopharm 42:975-985, 1999) have evaluated the scope of the nucleophilic aromatic fluorination of 2-substituted pyridine rings using the activated K [18F]F-K222 complex. As Me and methoxy groups are known to enhance the electron d. of an aromatic system by the +I and the +M effect, resp., SNAr is unlikely to occur. Until now, the effect of these substituents has not been studied towards the 18F-radiofluorination of substituted 2-nitropyridines by use of [18F]fluoride. Therefore, we have investigated the effect of methoxy and Me groups in 2-nitropyridines. The results showed that 3-methoxy-2-nitropyridine and 3-methyl-2-nitropyridine can efficiently be substituted by [18F]fluoride with high RCY’s (70-89%) in short reaction times (1-30 min) at a reaction temperature of 140 °C. Moreover, 3-methoxy-6-methyl-2-[18F]fluoropyridine was obtained from the corresponding nitro-precursor in a high yield of 81 ± 1% after 30 min at 140 °C. In case of 2-nitropyridines data indicates the effect of Me and methoxy groups on SNAr to be of minor importance. In the experiment, the researchers used many compounds, for example, 3-Hydroxy-6-methyl-2-nitropyridine (cas: 15128-90-2Quality Control of 3-Hydroxy-6-methyl-2-nitropyridine).
3-Hydroxy-6-methyl-2-nitropyridine (cas: 15128-90-2) belongs to pyridine derivatives. The ring atoms in the pyridine molecule are sp2-hybridized. The nitrogen is involved in the π-bonding aromatic system using its unhybridized p orbital. The lone pair is in an sp2 orbital, projecting outward from the ring in the same plane as the σ bonds. Reduced pyridines, namely tetrahydropyridines, dihydropyridines and piperidines, are found in numerous natural and synthetic compounds. The synthesis and reactivity of these compounds have often been driven by the fact many of these compounds have interesting and unique pharmacological properties. Quality Control of 3-Hydroxy-6-methyl-2-nitropyridine