Pyridine ring protonization

More powerful directing groups such as those based on amides and sulphonamides are successful with pyridines as with carboxylic rings, and will not be discussed separately. The enhanced acidity of pyridine ring protons makes the simple carboxylate substituent an ideal director of lithiation in pyridine systems . The pyridinecarboxylic acids 232-234 are deprotonated with BuLi and then lithiated with an excess of LiTMP all the substitution patterns are lithiated nicotinic acid 233 is lithiated in the 4-position (Scheme 113). The method provides a valuable way of introducing substituents into the picolinic, nicotinic and isonicotinic acid series. 

In the quinoline isosteres and their derivatives, the coupling constant between the pyridine ring protons a and /) to the nitrogen atom is usually ca. 4.5 Hz (value for quinoline is 4.1 Hz). 

The catalytic effect of the acid can be explained by protonation of either pyridine ring. Protonation of ring B (23) makes it more susceptible to nucleophilic attacks, while protonation of ring A (24) stabilizes the leaving group. 

The electrophilic substitution of thiophene is much easier than that of benzene thus, thiophene is protonated in aqueous sulphuric acid about 10 times more rapidly than benzene, and it is brominated by molecular bromine in acetic acid about 10 times more rapidly than benzene. Benzene in turn is between 10 and lo times more reactive than an uncharged pyridine ring to electrophilic substitution. 

Four multiplets between Sh = 7.46 and 9.18 indicate monosubstitution of the pyridine ring, either in the 2- or 3-position but not in the 4-position, since for a 4-substituted pyridine ring an AA XX system would occur. The position of the substituents follows from the eoupling eonstants of the threefold doublet at Sh = 7.46, whose shift is appropriate for a p-proton on the pyridine ring (A). 

In agreement with the previous data on the protonation site in azaindoles (76AHCS1, p. 529), an example of monoprotonation of 3-aryl substituted 6-azaindoles at the pyridine ring has been demonstrated by UV speetroseopy [88JCS(P2)1839]. 

UV spectrum changes dramatically. The salt causes maxima at 251 (4.16), 286 (4.16), 387 (3.56), and 473 (3.37) nm. NMR data for a sample in CF3COOD were presented. It is interesting to note that the nonmethylated derivatives of 130 and 131 are present in solution above pH 6.5 as betaines, forming a protonated pyridine ring and an olate group (91MI3). 

In the dihapto mode the pyridine ring can be protonated intermolecularly at nitrogen, or even intramolecularly deprotonated at carbon. The first evidence for metal C—N insertion is the reaction of the metallaaziridine complex (111) with homogeneity LiHBEt3 in THF at low temperature that yields (112) (Scheme 49).251-254 Experiments with carbon nucleophiles (RMgCl, MeLi) in place of LiHBEt3 have provided valuable information to allow discrimination between... 

The surface-enhanced Raman spectra (SERS) provide information about the extent of protonation of the species adsorbed at the silver/aqueous solution interface. The compounds investigated were 4-pyridyl-carbinol (1), 4-acetylpyridine (2), 3-pyridine-carboxaldehyde (3), isonicotinic acid (4), isonicotinamide (5), 4-benzoylpyridine (6), 4-(aminomethyl)pyridine (7) and 4-aminopyridine (8). For 1, the fraction of the adsorbed species which was protonated at -0.20 V vs. SCE varied with pH in a manner indicating stronger adsorption of the neutral than the cationic form. The fraction protonated increased at more negative potentials. Similar results were obtained with 3. For all compounds but 4, bands due to the unprotonated species near 1600 cm-1 and for the ring-protonated species near 1640 cm-1 were seen in the SERS spectra. 

In the present research, it was confirmed for compounds 1-3 that, in the normal Raman spectra of aqueous solutions of various pH, a band near 1600 cm-1 appears for the neutral pyridine and a band near 1640 cm-1 exists for the ring-protonated species. 

The poly(vinylpyridine) and poly(tert-butyl methacrylate) copolymers can easily be converted to either cationic or anionic polyelectrolytes by protonation of the pyridine rings or by base hydrolysis of the tert-butyl ester units, respectively. The highly branched structure of the molecules, in combination with the polyelectrolyte effect, should confer useful properties to these materials in solution for applications such as pH-sensitive reversible gels. 

Fig. 6.4 Reversible interconversion of amino acid and keto acid. Conjugation of the imine bond in the aldimine with the electron sink of the pyridine ring plus protonation of the pyridine nitrogen as well as the metal ion - all this results in weakening of the C-H bond of the amino acid residue. Thus, also catalyzed is a-proton exchange, racemization of a chiral center at the a-carbon atom and decarboxylation of the appropriate amino acid. ...

The rather high basic strength of 3,5-diazaindole [91] (p/sTa = 6T) is not due to the protonation of the imidazole ring (for benzimidazole p g = 5-53), but rather of the pyridine ring. Cation [92] is formed and this is stabilized by the same kind of resonance as... 

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